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Objective The natural history of urothelial carcinoma arising at the uretero-enteric junction (UEJ) is poorly defined, and the data guiding clinical management of these patients is limited. Therefore, we evaluated oncologic outcomes of patients treated for urothelial carcinoma at the UEJ. Methods Utilizing a multi-institutional database of patients treated with radical nephroureterectomy (RNU), we assessed the clinicopathologic parameters and oncologic outcomes of UEJ tumors compared with other upper tract urothelial carcinomas (UTUC). Survival analyses were performed to determine independent predictors of disease recurrence and cancer-specific mortality after RNU. Results The study included 1,363 patients, 921 men and 442 women with 36 months median follow-up after RNU. Compared with UTUC in the kidney or ureter, UEJ tumors ( n = 22) were more likely to demonstrate features of advanced disease, which were proved to be independent predictors of disease recurrence and cancer-specific mortality after RNU. The 5 year disease-free survival (DFS) and cancer-specific survival (CSS) rates were 25% and 39% in those with UEJ tumors vs. 69% and 73% in those with UTUC in the kidney or ureter ( P = 0.001 and P = 0.008, respectively). Conclusions UEJ tumors harbor features of locally advanced disease associated with high risk of systemic recurrence and death from cancer after RNU. Our findings suggest the need for integration of systemic therapy into the management paradigm of these patients.

Purpose: To examine the overall and stage-specific age-adjusted incidence, 5-year survival and mortality rates of bladder cancer (BCa) in the United States, between 1973 and 2009. Materials and methods: A total of 148,315 BCa patients were identified in the Surveillance, Epidemiology and End Results database, between years 1973 and 2009. Incidence, mortality, and 5-year cancer-specific survival rates were calculated. Temporal trends were quantified using the estimated annual percentage change (EAPC) and linear regression models. All analyses were stratified according to disease stage, and further examined according to sex, race, and age groups. Results: Incidence rate of BCa increased from 21.0 to 25.5/100,000 person-years between 1973 and 2009. Stage-specific analyses revealed an increase incidence for localized stage: 15.4-20.2 (EAPC: +0.5%, p < 0.001) and distant stage: 0.5-0.8 (EAPC: +0.7%, p = 0.001). Stage-specific 5-year survival rates increased for all stages, except for distant disease. No significant changes in mortality were recorded among localized (EAPC: -0.2%, p = 0.1) and regional stage (EAPC: -0.1%, p = 0.5). An increase in mortality rates was observed among distant stage (EAPC: +1.0%, p = 0.005). Significant variations in incidence and mortality were recorded when estimates were stratified according to sex, race, and age groups. Discussion: Albeit statistically significant, virtually all changes in incidence and mortality were minor, and hardly of any clinical importance. Little or no change in BCa cancer control outcomes has been achieved during the study period. (C) 2013 Elsevier Ltd. All rights reserved.

Item does not contain fulltext BACKGROUND: Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX). OBJECTIVE: To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa). DESIGN, SETTING, AND PARTICIPANTS: Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies. INTERVENTION: IBX (>/= 10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model. RESULTS AND LIMITATIONS: Any PCa and HGPCa were diagnosed in 46% (n=318) and 20% (n=137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p

Objective: To examine characteristics of robot-assisted (RARP) and open radical prostatectomy (ORP) patients. Patients and Methods: We relied on the Surveillance, Epidemiology, and End Results-Medicare-linked database and focused on prostate cancer patients between 2008 and 2009. In multivariable logistic regression analyses, we predicted RARP. Results: Of 5,915 patients, 3,476 (58.8%) underwent RARP and 2,439 (41.2%) ORP. Patients within intermediate (OR 1.4, p = 0.01) or highest (OR 1.5, p = 0.02) education strata and those treated by surgeons with a high volume (OR 2.2, p < 0.001) were more likely to undergo RARP. Conversely, those residing in rural areas (OR 0.7, p = 0.005) and those with clinical stage T2 or higher (OR 0.7, p = 0.006) were less likely to undergo RARP. Additionally, patients from the Southwest were less likely to undergo RARP (OR 0.4, p < 0.001), but those from the Northern Plains were more likely to undergo RARP (OR 1.4, p = 0.02) than their counterparts from the East. Finally, RARP patients were neither younger nor healthier than ORP patients. Conclusions: Several patient characteristics such as education, region of residence and population density affect the likelihood of RARP vs. ORP treatment. Similarly, clinical stage and surgeon characteristics also affect the assignment to one or other treatment modality.

Background: We assessed the distribution of site-specific metastases in patients with renal cell carcinoma (RCC) according to age. Moreover, we evaluated recommendations proposed by guidelines and focused specifically on bone and brain metastases. Patients and methods: Patients with metastatic RCC (mRCC) were abstracted from the Nationwide Inpatient Sample (1998–2007). Age was stratified into four groups

Background: To examine the use of open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN), as well as intraoperative and postoperative morbidity. Materials and methods: A retrospective cohort analysis of the Nationwide Inpatient Sample for years 1998-2007. Patients with non-metastatic kidney cancer who underwent OPN or LPN were identified. Propensity-based matching was performed to adjust for potential baseline differences between the two groups. The rates of intraoperative and postoperative complications, blood transfusions, length of stay, and in-hospital mortality were assessed for both procedures. Results: Overall, 7990 (93.9%) and 523 (6.1%) patients underwent OPN and LPN, respectively. Use of LPN increased 19-fold over the study period (P < 0.001). For OPN and LPN respectively, the following rates were recorded: blood transfusions, 9.3 vs. 3.8% (P < 0.001); intraoperative complications, 2.9 vs. 1.5% (P = 0.06); postoperative complications, 15.4 vs. 11.3% (P = 0.01); length of stay >= 5 days, 46.7 vs. 20.8% (P < 0.001); in-hospital mortality, 0.4 vs. 0.4% (P = 0.98). In multivariable logistic regression analyses, LPN patients were less likely to have a blood transfusion (odds ratio [OR]: 0.40, P < 0.001), to experience any postoperative complication (OR: 0.74, P = 0.03), and to be hospitalized for more than 5 days (OR: 0.32, P < 0.001). Post-propensity score matched analyses revealed virtually the same results. Conclusions: After adjustment for potential selection biases, LPN is associated with fewer adverse outcomes than OPN. However, the current results should be interpreted with caution, given the lack of tumor characteristics. Furthermore, statistical adjustment is not a substitute for a needed randomized trial. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

"Purpose: National Comprehensive Cancer Network practice guidelines indicate that pelvic lymph node dissection can be omitted at radical cystectomy in elderly patients. We examined the pelvic lymph node dissection rate in patients 80 years old or older and the impact of pelvic lymph node dissection on cancer specific and overall mortality in these patients. Materials and Methods: We examined the records of 11,183 patients treated with radical cystectomy in 17 Surveillance, Epidemiology and End Results registries. We performed univariate and multivariate Cox regression analysis to test the effect of pelvic lymph node dissection on cancer specific and overall mortality. Results: Overall pelvic lymph node dissection was omitted in 25% of patients, including 24.2% younger than 80 years and 30.8% 80 years old or older (p < 0.001). The 5-year rate of freedom from cancer specific mortality for pelvic lymph node dissection vs no pelvic lymph node dissection was 62.5% vs 59.9% in patients younger than 80 years, and 50.0% vs 46.1% in those 80 years old or older (p = 0.01 and 0.005, respectively). The 5-year rate of freedom from overall mortality for the same categories was 48.8% vs 43.9% and 28.3% vs 24.7% (p < 0.001 and 0.01, respectively). On multivariate analysis omitting pelvic lymph node dissection was associated with a 1.3-fold higher cancer specific rate at ages less than 80 and 80 years or greater (each p < 0.001). Omitting pelvic lymph node dissection was also associated with a 1.3-fold higher overall mortality rate, including 1.3 at ages less than 80 years and 1.2-fold at ages 80 years or greater (each p

Background Conditional survival (CS) provides better estimates of the survival probability at each follow-up time, and its usefulness has been proven in several solid malignancies. Objective To assess the changes in 5-yr CS rates after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to determine how well-established prognostic factors evolve over time. Design, setting, and participants We analysed data from 3544 patients treated with RNU at 15 international academic centres between 1989 and 2012. Intervention RNU. Outcomes measurements and statistical analysis Conditional intravesical recurrence-free (IVRFS), cancer-specific survival (CSS), and overall survival (OS) estimates were calculated using the Kaplan-Meier method. A multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality. Results and limitations The 5-yr bladder cancer recurrence-free survival, CSS, and OS rates were 54.9%, 72.2%, and 62.6%, respectively. Given a 1-, 2-, 3-, and 4-yr survivorship, the 5-yr conditional OS rates improved to 65.2%, 69.3%, 71.5%, and 73.0%, respectively. The 5-yr CS improvement was primarily noted among surviving patients with advanced-stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS, whereas the impact of age and gender increased with survivorship. No survival benefit was noted regarding the adjuvant chemotherapy status. Findings were confirmed upon multivariable analyses. Tumour location, the presence of carcinoma in situ, and the type of bladder cuff excision were continuously predictive for IVRFS whatever the survivorship. A limitation is the retrospective design. Conclusions CS analysis demonstrates that the patient risk profile evolves during the post-RNU follow-up. The probability of survival markedly increases over time in patients having high-stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS. Patient summary In this study, we found that the risk of intravesical recurrence, cancer-specific survival, and overall mortality evolves over the follow-up after surgery. Taking into account the survivorship provides better estimates of the survival probability at each follow-up time.

Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival.The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates.Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival.In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

Background: The role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial. Objective: The relationship between the number of removed lymph nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI. Design, setting, and participants: We examined data of 315 pN1 PCa patients treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at one tertiary care centre. All patients received adjuvant hormonal therapy with or without adjuvant radiotherapy (aRT). Outcome measurements and statistical analysis: Univariable and multivariable Cox regression analyses tested the relationship between RLN number and CSM rate, after adjusting to all available covariates. Survival estimates were based on the multivariable model; patients were stratified according to RLN number using points of maximum separation. Results and limitations: The average number of RLNs was 20.8 (median: 19; interquartile range: 14–25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs independently predicted lower CSM rate (hazard ratio [HR]: 0.93; p = 0.02). Other predictors of CSM were Gleason score 8–10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26; all p 0.006). The study is limited by its retrospective nature. Conclusions: In PCa patients with LNI, the removal of a higher number of LNs during RP was associated with improvement in cancer-specific survival rate. This implies that ePLND should be considered in all patients with a significant preoperative risk of harbouring LNI. Patient summary: We found that removing more lymph nodes during prostate cancer surgery can significantly improve cancer-specific survival in patients with lymph node invasion.

Introduction: To evaluate the incidence of carcinoma in situ (CIS) in patients treated with radical cystectomy (RC) due to bladder cancer and to assess its effect on recurrence and survival rates.Methods: The study focused on 1,128 consecutive nonmetastatic patients with bladder cancer treated with RC at a single tertiary care referral center from 1994 to 2014. The Kaplan-Meier method was used to compare recurrence, cancer-specific mortality (CSM), and overall mortality free rates in the overall population and in pTO pT2 and pT3 pT4 patients after stratifying according to the presence of CIS. Multivariable (MVA) Cox regression analyses tested the effect of the presence of CIS on survival outcomes. MVA competing risk analyses were performed to assess the effect of CIS on urothelial recurrence.Results: The presence of CIS was reported in 277 (24.6%) patients. During a median follow-up of 6 years, 355 recurrences, 377 CSM, and 468 overall mortality were reported. At MVA Cox regression analyses, the presence of concomitant CIS was not associated with any survival effect when the overall population was considered (all P >= 0.3). At MVA Cox regression analyses, there was no effect of CIS on survival outcomes in pT3 pT4 patients (all P > 0.2); on the contrary, the presence of CIS was associated with worse CSM in pTO pT2 patients only (hazard ratio [HR] = 1.82; CI: 1.01-3.29; P = 0.04). At MVA competing risk analyses predicting urothelial recurrence only, the presence of CIS was associated to an increased risk of urothelial recurrence in pTO pT2 patients (HR = 2.99; CI: 1.05-8.53; P = 0.04), pT3 pT4 patients (HR = 10.29; CI: 1.40-75.75; P = 0.02), and in the overall population (HR = 4.47; CI: 1.81-11.07; P = 0.001).Conclusion: An increased risk of developing urothelial recurrence only was recorded in patients diagnosed with CIS at RC. Physicians should consider this aspect ensuring a more severe follow-up schemes in patients who harbored this pathological feature. (C) 2017 Elsevier Inc. All rights reserved.

Introduction: Existing radical cystectomy (RC) perioperative mortality estimates may underestimate the contemporary rates due to more advanced age, more baseline comorbidities and potentially broader inclusion criteria for RC, relative to past criteria. Methods: Within the most recent Surveillance, Epidemiology, and End Results (SEER)-Medicare database we identified clinically nonmetastatic, muscle-invasive (T2eT4a) urothelial carcinoma of the urinary bladder (UCUB) patients, who underwent RC between 1991 and 2009. Mortality at 30- and 90-day after RC was quantified. Multivariable logistic regression analyses tested predictors of 90-day mortality. Results: Within 5207 assessable RC patients 30- and 90-day mortality rates were 5.2 and 10.6%, respectively. According to age 65e69, 70e79 and � 80 years, 90-day mortality rates were 6.4, 10.1 and 14.8% (p < 0.001). Additionally, 90-day mortality rates increased with increasing Charlson Comorbidity Index (CCI, 0, 1, 2 and � 3): 6.3, 10.3, 12.6 and 15.9% (p < 0.001). 90-day mortality rate in unmarried patients was 13.0 vs. 9.3% in married individuals (p < 0.001). In multivariable logistic regression analyses, advanced age, higher CCI, low socioeconomic status, unmarried status and non organ-confined stage were independent predictors of 90-day mortality (all p < 0.05). Conclusions: The contemporary SEER-Medicare derived 90-day mortality rates are substantially higher than previously reported estimates from centers of excellence, and even exceed previous SEER reports. More advanced age, higher CCI score, and other patient characteristics that distinguish the current population from others account for these differences. 2014 Elsevier Ltd. All rights reserved.

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

Contains fulltext : 153742.pdf (Publisher’s version ) (Closed access) BACKGROUND: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE: To assess prognostic factors in patients who received bacillus Calmette-Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >/= 70 yr, size >/= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >/= 70 yr with tumor size >/= 3 cm and 13% otherwise. CONCLUSIONS: T1G3 patients >/= 70 yr with tumors >/= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >/= 70 yr, tumor size >/= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

Background:Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status.Methods:We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes.Results:In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively.Conclusions:Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis. © 2014 Cancer Research UK.

Background Androgen deprivation therapy (ADT) might increase the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa).Design, setting, and participants Overall, 69 292 patients diagnosed with nonmetastatic PCa between 1995 and 2009 were abstracted from the Surveillance Epidemiology and End Results-Medicare database. Outcomes measurements and statistical analyses Patient in both treatment arms (ADT vs no ADT) were matched using propensity-score methodology. Ten-year AKI rates were estimated. Competing-risks regression analyses tested the association between ADT and AKI, after adjusting for the risk of death during follow-up.Patient summary The administration of gonadotropin-releasing hormone agonists, but not bilateral orchiectomy, increases the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa). These observations should help provide physicians with better patient selection to reduce the risk of AKI in PCa patients.Results and limitations Overall, the 10-yr AKI rates were 24.9% versus 30.7% for ADT-naive patients versus those treated with ADT, respectively (p < 0.001). When patients were stratified according to the type of ADT, the 10-yr AKI rates were 31.1% versus 26.0% for men treated with gonadotropin-releasing hormone (GnRH) agonists and bilateral orchiectomy, respectively (p < 0.001). In multivariable analyses, the administration of GnRH agonists (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.18-1.31; p < 0.001), but not bilateral orchiectomy (HR: 1.11; 95% CI, 0.96-1.29; p = 0.1), was associated with the risk of experiencing AKI. Our study is limited by its retrospective design.Conclusions ADT is associated with an increased risk of AKI in patients with nonmetastatic PCa. In particular, the administration of GnRH agonists, but not surgical castration, may substantially increase the risk of experiencing AKI. These observations should help provide physicians with better patient selection to reduce the risk of AKI.

Objectives: Local tumor destruction (LTD) is a recommended therapy alternative for localized TI renal cell carcinoma for patients who are unfit for surgery. We examined patterns of use and complication rates of LTD in a large population-based cohort. Materials and methods: Overall, data for 5,285 patients undergoing LTD for renal cell carcinoma were extracted from the Nationwide Inpatient Sample database from 2006 to 2010. We assessed patient and hospital characteristics, as well as postoperative complications, using International Classification of Diseases, Ninth Revision codes. The effect of patient and hospital characteristics on peri-interventional complications (overall or specific) was tested using univariable or multivariable logistic regression models. Results: Most patients were male (61.2%), aged 71 to 80 years (34.9%), and had 3 or more comorbidities (30.6%). Most LTDs were performed at urban (93.5%), teaching (57.7%), and low-volume (75.7%) hospitals. Overall complications were recorded in 15.4% of patients. In multivariable analyses adjusted for clustering, overall complications occurred more frequently in older, sicker patients who were treated at low-volume hospitals (all P < 0.05). Similar results were recorded when each complication category was addressed individually. Conclusions: In the current population-based cohort, complications of LTD occurred in 1 of 6 patients and were more frequent in individuals with advanced age or multiple comorbidities, or both, especially if LTDs were performed at lower-volume hospitals. (C) 2014 Elsevier Inc. All rights reserved.

Background Although therapeutic guidelines recommend the use of neoadjuvant chemotherapy before radical cystectomy (RC) in patients who have muscle-invasive bladder cancer (MIBC), this approach remains largely underused. One of the main reasons for this phenomenon might reside in concerns regarding the risk of morbidity and mortality associated with neoadjuvant chemotherapy. Objective To compare perioperative outcomes between patients receiving neoadjuvant chemotherapy and those treated with RC alone. Design, setting, and participants Relying on the Surveillance Epidemiology and End Results-Medicare-linked database, 3760 patients diagnosed with MIBC between 2000 and 2009 were evaluated. Intervention RC alone or RC plus neoadjuvant chemotherapy. Outcome measurements and statistical analysis Complications occurred within 30 and 90 d after surgery. Heterologous blood transfusions (HBTs), length of stay (LoS), readmission, and perioperative mortality were compared. To decrease the effect of unmeasured confounders associated with treatment selection, propensity score-matched analyses were performed. Results and limitations Overall, 416 (11.1%) of patients received neoadjuvant chemotherapy. Following propensity score matching, 416 (20%) and 1664 (80%) patients treated with RC plus neoadjuvant chemotherapy and RC alone remained, respectively. The 30-d complication, readmission, and mortality rates were 66.0%, 32.2%, and 5.3%, respectively. The 90-d complication, readmission, and mortality rates were 72.5%, 46.6%, and 8.2%, respectively. When patients were stratified according to neoadjuvant chemotherapy status, no significant differences were observed in the rates of complications, HBT, prolonged LoS, readmission, and mortality between the two groups (all p ≥ 0.1). These results were confirmed in multivariate analyses, where the use of neoadjuvant chemotherapy was not associated with higher risk of 30- and 90-d complications, HBT, prolonged LoS, readmission, and mortality (all p ≥ 0.1). Our study is limited by its retrospective nature. Conclusions The use of neoadjuvant chemotherapy is not associated with higher perioperative morbidity or mortality. These results should encourage wider use of neoadjuvant chemotherapy when clinically indicated. Patient summary Chemotherapy before radical cystectomy in patients with muscle-invasive bladder cancer does not increase the risk of complications or death. The use of chemotherapy should be strongly encouraged, as recommended by clinical guidelines, given its benefits. © 2014 European Association of Urology.

International audience; PURPOSE: We conceived and proposed a unique and optimized nomogram to predict cancer specific survival after radical nephroureterectomy in patients with upper tract urothelial carcinoma by merging the 2 largest multicenter data sets reported in this population. MATERIALS AND METHODS: The international and the French national collaborative groups on upper tract urothelial carcinoma pooled data on 3,387 patients treated with radical nephroureterectomy for whom full data for nomogram development were available. The merged study population was randomly split into the development cohort (2,371) and the external validation cohort (1,016). Cox regressions were used for univariable and multivariable analyses, and to build different models. The ultimate reduced nomogram was assessed using Harrell's concordance index (c-index) and decision curve analysis. RESULTS: Of the 2,371 patients in the nomogram development cohort 510 (21.5%) died of upper tract urothelial carcinoma during followup. The actuarial cancer specific survival probability at 5 years was 73.7% (95% CI 71.9-75.6). Decision curve analysis revealed that the use of the best model was associated with benefit gains relative to the prediction of cancer specific survival. The optimized nomogram included only 5 variables associated with cancer specific survival on multivariable analysis, those of age (p = 0.001), T stage (p

Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT(3)N(0) prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at 0.2 ng/mL within 2 or 3 years after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P =.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT(3)N(0) PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed. (C) 2013 Elsevier Inc.

Background: The risk of in-hospital mortality after cytoreductive nephrectomy (CNT) is non-negligible and may vary widely according to various patient and hospital characteristics and clinical contexts. Objective: To better elucidate the mechanisms underlying variability in operative mortality after CNT. Design, setting, and patients: Using the US-based Nationwide Inpatient Sample registry, a weighted estimate of 16 285 patients with metastatic renal cell carcinoma (mRCC) treated with CNT between 1998 and 2007 was made retrospectively. Outcome measurements and statistical analysis: Failure to rescue (FTR), defined as the number of deaths in patients who developed an adverse outcome during hospitalization. Univariable and multivariable logistic regression models were used. Results: Of all 16 285 mRCC patients who underwent a CNT, 31% had an occurrence of one complication or more. The overall FTR rate was 5% and differed significantly according to age (75 yr vs = 3 vs 0: 7.7% vs 4.8%), as well as hospital bed size (small vs large: 7.2% vs 5.3%, all p

The primary endpoint in trials of perioperative systemic therapy for urothelial carcinoma is 5-year overall survival (OS). A shorter-term endpoint could significantly speed the translation of advances into practice. We hypothesized that disease-free survival (DFS) could be a surrogate endpoint for OS in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). The study included 2,492 patients treated with RNU with curative intent for UTUC. 2/3-year DFS estimates were 78/73 %, and the 5-year OS estimate was 64 %. The overall agreements between 2- and 3-year DFS with 5-year OS were 85 and 87 %, respectively. Agreements were similar when analyzed in subgroups stratified by pathological stages, lymph node status, and adjuvant chemotherapy. The kappa statistic was 0.59 (95 % CI 0.55–0.63) for 2-year DFS/5-year OS and 0.64 (95 % CI 0.61–0.68) for 3-year DFS/5-year OS, indicating moderate reliability. The hazard ratio for DFS as a time-dependent variable for predicting OS was 11.5 (95 % CI 9.1–14.4), indicating a strong relationship between DFS and OS. In patients treated with RNU for UTUC, DFS and OS are highly correlated, regardless of tumor stage and adjuvant chemotherapy. While significant differences in DFS, assessed at 2 and 3 years, are highly likely to persist in OS at 5 years, marginal DFS advantages may not translate into OS benefit. External validation is necessary before accepting DFS as an appropriate surrogate endpoint for clinical trials investigating advanced UTUC patients.

Background: Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood. Objective: To analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non-muscle-invasive bladder cancer (NMIBC). Design, setting, and participants: We collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (= 20 yr), heavy short term (>= 20 CPD, = 20 CPD, >= 20 yr). The median follow-up in this retrospective study was 49 mo. Interventions: Transurethral resection of the bladder with or without intravesical instillation therapy. Outcome measurements and statistical analysis: Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes. Results and limitations: There was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p = 0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p < 0.001), progression (p < 0.001), and overall survival (p < 0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation > 10 yr reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52-0.84; p < 0.001) and progression (HR: 0.42; 95% CI, 0.22-0.83; p = 0.036) in multivariable analyses. The study is limited by its retrospective nature. Conclusions: Smoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.

International audience; BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a clinically heterogeneous disease that lacks high-quality trials that provide definitive prognostic markers. Insulin-like growth factor messenger RNA binding protein 3 (IMP3) has been associated with outcomes in urothelial carcinoma of the bladder but was not yet studied in UTUC. OBJECTIVE: To evaluate the association of the oncofetal protein IMP3 with oncologic outcomes in patients with UTUC treated with radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS: We investigated the expression of IMP3 and its association with clinical outcomes using tissue microarrays constructed from 622 patients treated with RNU at seven international institutions between 1991 and 2008. INTERVENTION: All patients were diagnosed with UTUC and underwent RNU. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Uni- and multivariable Cox regression analyses evaluated the association of IMP3 protein expression with disease recurrence, cancer-specific mortality, and all-cause mortality. RESULTS AND LIMITATIONS: IMP3 was expressed in 12.2% of patients with UTUC (n=76). The expression was tumor specific and correlated with higher stages/grades. Within a median follow-up of 27 mo (interquartile range [IQR]: 12-53), 191 patients (25.4%) experienced disease recurrence, and 165 (21.9%) died of the disease. Patients with IMP3 demonstrated significantly worse recurrence-free survival (27.4% vs 75.1%; p\textless0.01), cancer-specific survival (34.5% vs 78.9%; p\textless0.01), and overall survival (15.6% vs 64.8%; p\textless0.01) at 5 yr compared with those without IMP3. In multivariable Cox regression analyses, which adjusted for the effects of standard clinicopathologic features, IMP3expression was independently associated with disease recurrence (hazard ratio [HR]: 1.87; p\textless0.01), cancer-specific mortality (HR: 2.15; p\textless0.01), and all-cause mortality (HR: 2.07; p\textless0.01). Major limitations include the retrospective design and relatively short follow-up time. CONCLUSIONS: IMP3 expression is independently associated with disease recurrence, cancer-specific mortality, and all-cause mortality in UTUC. IMP3 may help improve risk stratification and prognostication of UTUC patients treated with RNU.

The presence of positive soft tissue surgical margins (STSM) at radical cystectomy (RC) is rare. Although some patients with STSM experience disease recurrence rapidly, some have long-term local disease control. We sought to describe the oncologic outcomes, identify predictors, and assess the impact of location and multifocality in patients with positive STSMs at RC. We retrospectively collected the data of 4,335 patients treated with RC and pelvic lymphadenectomy at 11 academic centers from 1981 to 2008. STSM was defined as the presence of tumor at inked areas of soft tissue on the RC specimen. Univariate and multivariate Cox regression models addressed recurrence-free survival and cancer-specific survival after surgery. STSM were identified in 231 patients (5 %). Actuarial recurrence-free survival estimates at 2 and 5 years after RC were 26 +/- A 3 and 21 +/- A 3 %, respectively. Actuarial cancer-specific survival estimates at 2 and 5 years after RC were 33 +/- A 3 and 25 +/- A 4 %, respectively. Higher body mass index (p = 0.050), higher tumor stage (p = 0.017), presence of grade 3 disease (p = 0.046), lymphovascular invasion (p = 0.003), and lymph node involvement (p = 0.003) were all independently associated with disease recurrence. Furthermore, higher tumor stage (p = 0.015), lymphovascular invasion (p = 0.006), and lymph node involvement (p = 0.006) were independently associated with cancer specific mortality. Location and multifocality of STSM were not associated with outcomes. Although most patients with STSM at RC had poor outcomes, more than one-fifth had durable cancer control. Pathologic features associated with disease recurrence in the general RC population also stratify patients with STSM into differential risk groups.

Purpose: The role of lymph node dissection is still controversial in patients treated with radical nephroureterectomy for upper tract urothelial cancer. We developed a pathological nodal staging model that allows quantification of the likelihood that a patient with pathologically node negative disease has, indeed, no lymph node metastasis. Materials and Methods: We analyzed data on 814 patients treated with radical nephroureterectomy and lymph node dissection, and estimated the sensitivity of pathological nodal staging using a beta-binomial model. We developed a pathological nodal staging score that represents the probability that a case is correctly staged as node negative. Results: A median of 5 lymph nodes (range 1 to 46) was removed and 593 patients (73%) had pN0 disease. The probability of missing lymph node metastasis decreased as the number of nodes examined increased. If only a single node was examined, 44% of patients would have been misclassified as having pN0 disease while harboring lymph node metastasis. Even when 5 nodes were examined, 12% of patients would have been misclassified. The proportion of those with a positive node increased with advancing pathological T stage and lymphovascular invasion. Patients with pT0-Ta-Tis-T1/lynaphovascular invasion had more than a 95% chance of correct pathological nodal staging with 2 examined nodes. However, if a patient had pT3-T4 and positive lymphovascular invasion, even 20 examined lymph nodes did not attain 95% accuracy. Conclusions: Lymph node dissection provides more accurate staging and prediction of survival. The number of examined nodes needed for adequate staging depends on pT stage and lymphovascular invasion. We developed a tool to estimate the likelihood of false-negative lymph node metastasis, which could help refine clinical decision making regarding the administration of adjuvant chemotherapy.

What's known on the subject? and what does the study add?: Radical nephroureterectomy (RNU), the standard of care treatment for high-risk urothelial carcinoma of the upper tract (UTUC), results in loss of a renal unit. Loss of renal function decreases eligibility for systemic chemotherapies and results in decreased overall survival in various malignancies. The study shows that only a small proportion of patients had a preoperative renal function that would allow cisplatin-based chemotherapy. Moreover, eGFR significantly decreased after RNU, thereby lowering the rate of cisplatin eligibility to only 16 and 52% of patients based on the thresholds of 60 and 45 mL/min/1.73 m(2) , respectively. Taken together with the rest of the literature, the findings of the study support the use of cisplatin-based chemotherapy, when indicated, in the neoadjuvant rather than adjuvant setting.To report (i) the estimated glomerular filtration rate (eGFR) changes in patients undergoing radical nephro-ureterectomy (RNU) for upper tract urothelial carcinoma (UTUC); (ii) the rate of change in eGFR in patients eligible for cisplatin-based chemotherapy; and (iii) the association of preoperative, postoperative and rate of change of renal function variables with survival outcomes.We performed a retrospective analysis of 666 patients treated with RNU for UTUC at seven international institutions from 1994 to 2007. The eGFR was calculated at baseline and at 3-6 months (Modification of Diet in Renal Disease formula (MDRD) and Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EP) equations).The median (interquartile range) eGFR decreased by 18.2 (8-12)% after RNU. A total of 37% of patients had a preoperative eGFR ≥ 60 mL/min/1.73 m(2) , which decreased to 16% after RNU (P0.001); 72% of patients had a preoperative eGFR ≥ 45 mL/min/1.73 m(2) , which decreased to 52% after RNU (P0.001). The distributions were similar when analyses were restricted to patients with locally advanced disease (pT3-pT4) and/or lymph node metastasis. Patients older than the median age of 70 years were more likely to have a decrease in eGFR after RNU (P0.001). None of the renal function variables was associated with clinical outcomes such as disease recurrence, cancer-specific and overall mortality; however, when analyses were restricted to patients who had no adjuvant chemotherapy and did not experience disease recurrence (n = 431), a preoperative eGFR ≥ 60 mL/min/1.73 m(2) (P = 0.03) and a postoperative eGFR ≥ 45 mL/min/1.73 m(2) (P = 0.04) were associated with better overall survival in univariable analyses.In patients who had UTUC, eGFR was low and furthermore, it significantly decreased after RNU. Renal function did not affect cancer-specific outcomes after RNU.

Background: There is a lack of consensus regarding the optimal approach to the bladder cuff during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Objectives: To compare the oncologic outcomes following RNU using three different methods of bladder cuff management. Design, setting, and participants: Retrospective analysis of 2681 patients treated with RNU for UTUC at 24 international institutions from 1987 to 2007. Intervention: Three methods of bladder cuff excision were performed: transvesical, extravesical, and endoscopic. Outcome measurements and statistical analysis: Univariable and multivariable models tested the effect of distal ureter management on intravesical recurrence, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results and limitations: Of the 2681 patients, 1811 (67.5%) underwent the transvesical approach; 785 (29.3%), the extravesical approach; and 85 (3.2%), the endoscopic approach. There was no difference in terms of RFS, CSS, and OS among the three distal ureteral management approaches. Patients who underwent the endoscopic approach were at significantly higher risk of intravesical recurrence compared with those who underwent the transvesical (p = 0.02) or extravesical approaches (p = 0.02); the latter two groups did not differ from each other (p = 0.40). Actuarial intravesical RFS estimates at 2 and 5 yr after RNU were 69% and 58%, 69% and 51%, and 61% and 42% for the transvesical, extravesical, and endoscopic approaches, respectively. In multivariate analyses, distal ureteral management (p = 0.01), surgical technique (open vs laparoscopic; p = 0.02), previous bladder cancer (p < 0.001), higher tumor stage (trend; p = 0.01), concomitant carcinoma in situ (CIS) (p < 0.001), and lymph node involvement (trend; p < 0.001) were all associated with intravesical recurrence. Excluding patients with history of previous bladder cancer, all variables remained independent predictors of intravesical recurrence. Conclusions: The endoscopic approach was associated with higher intravesical recurrence rates. Interestingly, concomitant CIS in the upper tract is a strong predictor of intravesical recurrence after RNU. The association of laparoscopic RNU with intravesical recurrence needs to be further investigated. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Introduction Many patients diagnosed with localized prostate cancer (PCa) are presented with several treatment modalities, which may require time to understand these options before making an informed decision regarding treatment. Aim The aim of this study was to compare the effect of radical prostatectomy (RP) delay on postoperative functional outcomes and mortality in a North American population‐based cohort. Methods Overall, 17,153 men treated with RP for non‐metastatic clinical stage T1–2, low‐grade PCa between years 1995 and 2005 within the U.S. Surveillance, Epidemiology, and End Results Medicare‐linked database were abstracted. Main Outcome Measures The effect of treatment delay (from PCa diagnosis to RP of >3 months) on pathological upstaging at surgery (≥pT3) and postoperative functional outcomes (urinary incontinence and erectile dysfunction) was examined using logistic regression analyses. The 10‐year PCa mortality rates were computed using cumulative incidence rates. Results Overall, 2,576 (15%) patients underwent RP > 3 months after diagnosis. A treatment delay of >3 months was associated with a 24% and 33% higher rate of erectile dysfunction diagnosis and procedure, respectively (both P ≤ 0.001). Treatment delay was also associated with 6% higher rate of urinary incontinence procedure ( P = 0.01). Furthermore, a dose‐response effect was detected with respect to increasing durations of RP delay (≤3 vs. 3–5 vs. 5–9 vs. ≥9 months) the rates of erectile dysfunction and urinary incontinence diagnoses/procedures. Treatment delay was not associated with pathological upstaging and PCa mortality. Conclusions Customarily, the timing of RP following biopsy is dictated by tumor aggressiveness. In general, patients with more unfavorable characteristics are operated sooner. This may obliterate the potential detriments of delayed RP. The treatment delay between biopsy and RP may result in more extensive periprostatic tissue resection and may adversely affect postoperative continence and erectile function. Sun M, Abdollah F, Hansen J, Trinh Q‐D, Bianchi M, Tian Z, Briganti A, Shariat SF, Montorsi F, Perrotte P, and Karakiewicz PI. Is a treatment delay in radical prostatectomy safe in individuals with low‐risk prostate cancer? J Sex Med 2012;9:2961–2969.

Background: The objective of this study was to examine the rates of blood transfusions, prolonged length of stay, intraoperative and postoperative complications, as well as in-hospital mortality, stratified according to institutional academic status in patients undergoing radical cystectomy (RC). Methods: Within the Health Care Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients in whom RC was performed between 1998 and 2007. Multivariable logistic regression analyses were fitted to predict the likelihood of blood transfusions, prolonged length of stay, intraoperative and postoperative complications, and in-hospital mortality. Covariates included age, race, gender, Charlson Comorbidity Index (CCI), hospital region, insurance status, annual hospital caseload (AHC), year of surgery and urinary diversion. Results: Overall, 12 262 patients underwent RC. Of those, 7892 (64.4%) were from academic institutions. Patients treated at academic institutions were younger and healthier at baseline (all p < 0.001). RCs performed at academic institutions were associated with fewer postoperative complications (28.8% vs. 32.9%, p < 0.001), shorter length of stay (54.0% vs. 56.2%, p = 0.02) and lower in-hospital mortality rates (2.1 vs. 3.0%, p = 0.002). In multivariable analyses, patients who underwent RC at an academic hospital were 12% less likely to succumb to postoperative complications (odds ratio=0.88, p = 0.003). Interpretation: Even after adjusting for AHC, RCs performed at academic institutions are associated with better postoperative outcomes than RCs performed at non-academic institutions. From a public health prospective, performing RCs at academic institutions may help reduce costs associated with the management of complications and prolonged length of stay. © 2012 Canadian Urological Association.

Aim of study: To examine the impact of survival probability according to duration of survivorship following radical cystectomy (RC) in patients diagnosed with urothelial carcinoma of the urinary bladder (UCUB). Methods: Overall, 4991 UCUB patients who underwent RC were abstracted. The cumulative survival estimates were used to generate conditional survival rates. Cox regression analyses were performed for prediction of cancer-specific mortality (CSM), according to duration of survivorship. Results: The five-year CSM-free survival rate was 63.9% at RC, and increased to 71.0%, 77.5%, 81.7%, 85.9% and 86.3% in patients who survived >= 1, 2, 3, 4 and 5 years, respectively. Patients with pT2-4 disease benefitted from the highest increase in survivorship two years after RC. The same findings were recorded according to patients' nodal status. Conclusion: The survival of the first two years after RC markedly improves individual patient prognosis. The prognostic gains differ according to patient and tumour characteristics. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

Purpose: Discharge patterns, including rates of prolonged length of stay and transfer to a facility, were evaluated in the context of radical cystectomy. Materials and Methods: Within the Nationwide Inpatient Sample we focused on radical cystectomy performed between 1998 and 2007. Multivariable logistic regression analyses predicting the likelihood of prolonged length of stay or transfer to a facility were performed. Results: Overall 11,876 eligible radical cystectomy cases were identified. The rates of prolonged length of stay decreased from 59% in the early period (1998 to 2001) to 50% in the late period (2005 to 2007, p < 0.001) while the rates of transfer to a facility remained stable (14%). On multivariable analyses adjusted for clustering, prolonged length of stay was more frequently recorded in patients from low annual caseload hospitals (OR 1.42, p < 0.001), as well as in Medicaid and Medicare patients (OR 1.66 and 1.17, respectively, all p < 0.01). Similarly rates of transfer to a facility were significantly higher for patients from low annual caseload hospitals (OR 1.81, p < 0.001) and for those with Medicaid or Medicare (OR 2.18 and 1.54, respectively, all p < 0.001), as well as for patients treated at nonacademic institutions (OR 1.31, p < 0.001). Conclusions: It is encouraging that the rates of prolonged length of stay have decreased while the rates of transfer to a facility remained stable. However, it is worrisome that individuals treated at low annual caseload centers as well as those with Medicare and Medicaid insurance experience less favorable discharge patterns.

Background: Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined. Objective: To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP. Design, setting, and participants: This is a retrospective, international, multi-institutional cohort analysis. There was amedian follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers. Intervention: Open SRP. Measurements: BCR after SRP was defined as a serum prostate-specific antigen (PSA) >= 0.1 or >= 0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancerspecific death. Results and limitations: Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period. Conclusions: In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in > 75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Background: Initial treatment options for low-risk clinically localized prostate cancer (PCa) include radical prostatectomy (RP) or observation. Objective: To examine cancer-specific mortality (CSM) after accounting for other-cause mortality (OCM) in PCa patients treated with either RP or observation. Design, setting, and participants: Using the Surveillance Epidemiology and End Results Medicare-linked database, a total of 44 694 patients >= 65 yr with localized (T1/2) PCa were identified (1992-2005). Intervention: RP and observation. Measurements: Propensity-score matching was used to adjust for potential selection biases associated with treatment type. The matched cohort was randomly divided into the development and validation sets. Competing-risks regression models were fitted and a competing-risks nomogram was developed and externally validated. Results and limitations: Overall, 22 244 (49.8%) patients were treated with RP versus 22450 (50.2%) with observation. Propensity score-matched analyses derived 11 669 matched pairs. In the development cohort, the 10-yr CSM rate was 2.8% (2.3-3.5%) for RP versus 5.8% (5.0-6.6%) for observation (absolute risk reduction: 3.0%; relative risk reduction: 0.5%; p < 0.001). In multivariable analyses, the CSM hazard ratio for RP was 0.48 (0.38-0.59) relative to observation (p < 0.001). The competing-risks nomogram discrimination was 73% and 69% for prediction of CSM and OCM, respectively, in external validation. The nature of observational data may have introduced a selection bias. Conclusions: On average RP reduces the risk of CSM by half in patients aged >= 65 yr, relative to observation. The individualized protective effect of RP relative to observation may be quantified with our nomogram. Crown Copyright (C) 2011 Published by Elsevier B.V. on behalf of European Association of Urology. All rights reserved.

Context: Numerous predictive and prognostic tools have recently been developed for risk stratification of prostate cancer (PCa) patients who are candidates for or have been treated with radical prostatectomy (RP). Objective: To critically review the currently available predictive and prognostic tools for RP patients and to describe the criteria that should be applied in selecting the most accurate and appropriate tool for a given clinical scenario. Evidence acquisition: A review of the literature was performed using the Medline, Scopus, and Web of Science databases. Relevant reports published between 1996 and January 2010 identified using the keywords prostate cancer, radical prostatectomy, predictive tools, predictive models, and nomograms were critically reviewed and summarised. Evidence synthesis: We identified 16 predictive and 22 prognostic validated tools that address a variety of end points related to RP. The majority of tools are prediction models, while a few consist of risk-stratification schemes. Regardless of their format, the tools can be distinguished as preoperative or postoperative. Preoperative tools focus on either predicting pathologic tumour characteristics or assessing the probability of biochemical recurrence (BCR) after RP. Postoperative tools focus on cancer control outcomes (BCR, metastatic progression, PCa-specific mortality [PCSM], overall mortality). Finally, a novel category of tools focuses on functional outcomes. Prediction tools have shown better performance in outcome prediction than the opinions of expert clinicians. The use of these tools in clinical decision-making provides more accurate and highly reproducible estimates of the outcome of interest. Efforts are still needed to improve the available tools' accuracy and to provide more evidence to further justify their routine use in clinical practice. In addition, prediction tools should be externally validated in independent cohorts before they are applied to different patient populations. Conclusions: Predictive and prognostic tools represent valuable aids that are meant to consistently and accurately provide most evidence-based estimates of the end points of interest. More accurate, flexible, and easily accessible tools are needed to simplify the practical task of prediction. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

OBJECTIVE To examine the stage migration patterns in patients treated with radical prostatectomy (RP) for prostate cancer in Europe and in the USA in the last 20 years. PATIENTS AND METHODS Between 1988 and 2005, RP was performed in 11 350 men: 5739 from Europe and 5611 from the USA. Independent-samples t-test and the chi-square test were, respectively, used for comparisons of means and proportions. The trend test was used to test the statistical significance of trends in proportions over time. RESULTS Temporal patterns in patients’ age, stage and PSA level at presentation were similar on both continents. Conversely, temporal patterns in Gleason sum distribution differed. In the USA, the rate of biopsy Gleason sums of 2–5 decreased from 32.8% to 0.2% (P

Many investigators suggested that obesity predisposes to adverse prostate cancer characteristics and outcomes. We tested the effect of obesity on the rate of aggressive prostate cancer at either prostate biopsy or radical prostatectomy (RP). Clinical and pathological data were available for 1,814 men. Univariable and multivariable logistic regression models addressed the rate of high grade prostate cancer (HGPCa) at either biopsy or final pathology. Clinical stage, prostate-specific antigen (PSA), percentage of free PSA and prostate volume were the base predictors. All models were fitted with and without body mass index (BMI), which quantified obesity. BMI and its reciprocal (InvBMI) were coded as cubic splines to allow nonlinear effects. Predictive accuracy (PA) was quantified with area under curve estimates, which were subjected to 200 bootstrap resamples to reduce overfit bias. Gains in PA related to the inclusion of BMI were compared using the Mantel-Haenszel test. HGPCa at biopsy was detected in 562 (31%) and HGPCa at RP pathology was present in 931 (51.3%) men. In either univariable or multivariable models predicting HGPCa at biopsy, BMI or InvBMI failed to respectively reach statistical significance or add to multivariable PA (BMI gain =0%, p=1.0; InvBMI gain =-0.2%,p=0.9). Conversely, in models predicting HGPCa at RP, BMI and InvBMI represented independent predictors but failed to increase PA (BMI gain =0.7%, p=0.6; InvBMI gain =0.5, p=0.7%). Obesity does not predispose to more aggressive prostate cancer at biopsy. Similarly, obesity does not change the ability to identify those who may harbor HGPCa at RP. (c) 2007 Wiley-Lissy Inc. Many investigators suggested that obesity predisposes to adverse prostate cancer characteristics and outcomes. We tested the effect of obesity on the rate of aggressive prostate cancer at either prostate biopsy or radical prostatectomy (RP). Clinical and pathological data were available for 1,814 men. Univariable and multivariable logistic regression models addressed the rate of high grade prostate cancer (HGPCa) at either biopsy or final pathology. Clinical stage, prostate-specific antigen (PSA), percentage of free PSA and prostate volume were the base predictors. All models were fitted with and without body mass index (BMI), which quantified obesity. BMI and its reciprocal (InvBMI) were coded as cubic splines to allow nonlinear effects. Predictive accuracy (PA) was quantified with area under curve estimates, which were subjected to 200 bootstrap resamples to reduce overfit bias. Gains in PA related to the inclusion of BMI were compared using the Mantel-Haenszel test. HGPCa at biopsy was detected in 562 (31%) and HGPCa at RP pathology was present in 931 (51.3%) men. In either univariable or multivariable models predicting HGPCa at biopsy, BMI or InvBMI failed to respectively reach statistical significance or add to multivariable PA (BMI gain =0%, p=1.0; InvBMI gain =-0.2%,p=0.9). Conversely, in models predicting HGPCa at RP, BMI and InvBMI represented independent predictors but failed to increase PA (BMI gain =0.7%, p=0.6; InvBMI gain =0.5, p=0.7%). Obesity does not predispose to more aggressive prostate cancer at biopsy. Similarly, obesity does not change the ability to identify those who may harbor HGPCa at RP. (c) 2007 Wiley-Lissy Inc.

Objectives: Seminal vesicle preservation may have a beneficial impact on erectile and urinary function after radical prostatectomy (RP). We hypothesized that contemporary patients, at very low risk of seminal vesicle invasion (SVI), can be highly accurately identified with an equally contemporary SVI nomogram. Materials and methods: A nomogram predicting SVI was developed in a cohort study of 666 men diagnosed with 10 or more biopsy cores and treated with RP. Biopsy Gleason sum, prostate -specific antigen, clinical stage, and percentage of positive cores represented predictors in multivariable logistic regression models and formed the basis for the nomogram. The regression coefficient-based nomogram was then externally validated in a split-saMple cohort of 230 patients. This cohort also served for a head-to-head comparison of external validity of the novel nomogram with two existing tools, namely Partin's SVI predictions and Koh's SVI nomogram. Results: Split-sample validation of the novel SVI nomogram demonstrated 79.2% accuracy versus 75.6% for Partin versus 77.7% for Koh. Our nomogram cutoff of 3% or less had 96.2% negative predictive value for identifying men at very low risk of SVI. This cutoff could have safely allowed omitting the removal of seminal vesicles in 45.2% of RP candidates, if incorrect classification of 1.7% of patients was judged acceptable. Conclusions: The potential benefits of SV preservation can be safely accomplished in virtually 50% of contemporary men subjected to RP, if our tool's predictions are applied. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. Objectives: Seminal vesicle preservation may have a beneficial impact on erectile and urinary function after radical prostatectomy (RP). We hypothesized that contemporary patients, at very low risk of seminal vesicle invasion (SVI), can be highly accurately identified with an equally contemporary SVI nomogram. Materials and methods: A nomogram predicting SVI was developed in a cohort study of 666 men diagnosed with 10 or more biopsy cores and treated with RP. Biopsy Gleason sum, prostate -specific antigen, clinical stage, and percentage of positive cores represented predictors in multivariable logistic regression models and formed the basis for the nomogram. The regression coefficient-based nomogram was then externally validated in a split-saMple cohort of 230 patients. This cohort also served for a head-to-head comparison of external validity of the novel nomogram with two existing tools, namely Partin's SVI predictions and Koh's SVI nomogram. Results: Split-sample validation of the novel SVI nomogram demonstrated 79.2% accuracy versus 75.6% for Partin versus 77.7% for Koh. Our nomogram cutoff of 3% or less had 96.2% negative predictive value for identifying men at very low risk of SVI. This cutoff could have safely allowed omitting the removal of seminal vesicles in 45.2% of RP candidates, if incorrect classification of 1.7% of patients was judged acceptable. Conclusions: The potential benefits of SV preservation can be safely accomplished in virtually 50% of contemporary men subjected to RP, if our tool's predictions are applied. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Objectives: We hypothesized that the number and/or percentage of positive cores, proxies of tumor volume, could improve the ability to predict pathologic stages and/or biochemical recurrence (BCR). To test this hypothesis, we examined radical retropubic prostatectomy (RRP) data from three centers on two continents. Material and methods: Clinical data from men undergoing RRP at three different institutions were used to predict pathologic stages and BCR. Univariable and multivariable logistic analyses and Cox regression analyses were used. Predictive accuracy (PA) was assessed with the area under the receiver operating characteristics curve estimates, which were subjected to 200 bootstraps to reduce overfit bias. The statistical significance of PA gains was assessed with the Mantel-Haenszel test. Results: The number and the percentage of positive cores were independent predictors of virtually all pathologic stage outcomes and of BCR. In PA analyses, the percentage of positive cores improved the PA of pathologic stage predictions and of BCR predictions between 0.06% and 1.49%. Conversely, the number of positive cores improved the PA of pathologic stage predictions and of BCR predictions between 0.36% and 1.14%. Conclusions: The information derived from biopsy cores is important and can improve the ability to predict pathologic stage and BCR. It appears that the percentage of cores is most helpful in stage predictions. Conversely, the number of cores appears to improve mostly BCR predictions. Consideration of both variables might not be helpful because of the similarity of information they encode. (c) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Objective To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. Patients and Methods The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from = 7 or from 7 to >= 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. Results Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. Conclusion Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options. Objective To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. Patients and Methods The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from = 7 or from 7 to >= 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. Results Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. Conclusion Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.

Purpose: We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort. Methods: Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots. Results: Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%. Conclusions: We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.

Objective To assess the accuracy and generalizability of the preand postoperative Karakiewicz nomograms for predicting cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC). Patients and Methods This retrospective study included 3231 patients from European and US centres, who were treated by radical or partial nephrectomy for RCC between 1992 and 2010. Prognostic scores for each patient were calculated and the primary endpoint was CSS. Discriminating ability was assessed by Harrell's c-index for censored data. The 'validation by calibration' method proposed by Van Houwelingen was used for checking the calibration of covariate effects. Calibration was graphically explored. Results Local and systemic symptoms were present in 23.2% and 9.1% of the patients, respectively. The median follow-up (FU) was 49 months. At the last FU, 408 cancer-related deaths were recorded, Kaplan-Meier estimates of CSS (with 95% confidence intervals [CIs]) at 5 and 10 years were 0.86 (0.84-0.87) and 0.77 (0.75-0.80), respectively. Both nomograms discriminated well. Stratified c-indices for CSS were 0.784 (95% CI 0.753-0.814) for the preoperative nomogram, and 0.842 (95% CI 0.816-0.867) for the postoperative one, with a significant difference between the two values (P < 0.001). The covariate-based predictions on our data for both nomograms were valid. The calibration plots showed no relevant departures from ideal predictions. Conclusions The results suggest that the postoperative Karakiewicz nomogram discriminates substantially better than the preoperative one. These nomogram-based predictions may be used as benchmark data for pretreatment and postoperative decision-making in patients at various stages of RCC.