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Objective: To compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view., Patients and Methods: Clinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient., Results: A VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study., Conclusions: Accuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The Albumin-Globulin Ratio (AGR; albumin/total protein - albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB., Material and Methods: We conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA)., Results: Overall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1-1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1-1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07-1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy., Conclusion: pAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation., Competing Interests: Conflicts of interest All authors have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: TaG3 bladder cancer is an under-investigated disease and because of its rarity it is commonly studies together with T1G3 disease. We sought to exclusively study TaG3 disease and to determine the factors associated with disease progression., Material and Method: We retrospectively studied patients with primary TaG3 bladder cancer. Progression to ≥pT1 and pT2 were analyzed using Cox and competing-risk regression analyses., Results: Of 3,505 consecutive patients with nonmuscle invasive bladder cancer, 285 patients had primary TaG3 without concomitant carcinoma in-situ. Progression to ≥pT1 occurred in 21 patients (7.4%). In a multivariable competing-risk regression analysis, intravesical Bacillus Calmette-Guerin (BCG) was significantly associated with a lower risk of progression to ≥pT1 (HR 0.23, 95%CI 0.08-0.64, P = 0.005). Recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥pT1 (HR 7.81, 95%CI 2.50-24.44, P < 0.001). Progression to ≥T2 was observed in 9 patients (3.2%). In univariable competing-risk regression analyses, intravesical BCG was significantly associated with a lower risk of progression to ≥pT2 (HR 0.11, 95%CI 0.04-0.47, P = 0.003). On the other hand, recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥T2 (HR 7.12, 95%CI 1.50-33.77, P = 0.013). In a subgroup of 199 patients who were treated with BCG, there was no statistically significant association between tumor recurrence in the 1 st year of diagnosis and stage progression to ≥pT1 (P = 0.14) or ≥pT2(P = 0.19)., Conclusion: Patients with TaG3 bladder cancer are considered high risk but if appropriately treated with BCG that risk is considerably mitigated. Our data support that TaG3 without concomitant carcinoma in-situ should not be considered as aggressive as T1G3 as it has a lower risk of progression to muscle-invasive bladder cancer. Recurrence in the first year after diagnosis is the strongest predictor of progression to muscle-invasive bladder cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Often contraindicated because of the theoretical risk of progression based on the dogma of hormone dependent prostate cancer (CaP), testosterone replacement therapy (TRT) is increasingly discussed and proposed for hypogonadal patients with localized CaP. To perform a systematic literature review to determine the relationship between TRT and the risk of CaP with a focus on the impact of TRT in the setting of previous or active localized CaP. As of October 15, 2019, systematic review was performed via Medline Embase and Cochrane databases in accordance with the PRISMA guidelines. All full text articles in English published from January 1994 to February 2018 were included. Articles were considered if they reported about the relationship between total testosterone or bioavailable testosterone and CaP. Emphasis was given to prospective studies, series with observational data and randomized controlled trials. Articles about the safety of the testosterone therapy were categorized by type of CaP management (active surveillance or curative treatment by radical prostatectomy, external radiotherapy or brachytherapy). Until more definitive data becomes available, clinicians wishing to treat their hypogonadal patients with localized CaP with TRT should inform them of the lack of evidence regarding the safety of long-term treatment for the risk of CaP progression. However, in patients without known CaP, the evidence seems sufficient to think that androgen therapy does not increase the risk of subsequent discovery of CaP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To evaluate the expression pattern and prognostic role of the urokinase-type plasminogen activator (uPA) system in patients who underwent radical nephroureterectomy (RNU) for nonmetastatic upper tract urothelial carcinoma (UTUC)., Methods: A total of 732 patients who were treated with RNU for clinically nonmetastatic UTUC comprised our analytical cohort. Immunohistochemical staining of uPA, uPA receptor (uPAR) and uPA inhibitor (PAI-1) was performed using Murine IgG1 monoclonal antibodies. Outcomes of interest were recurrence-free survival, cancer-specific survival, and overall survival., Results: The median age of the patients was 69.8 years and 56.6% of them were males. Overall, overexpression of uPA, uPAR, and PAI-1 was observed in 292 (39.9%), 346 (47.3%), and 345 (47.1%) patients, respectively. The uPA system components showed a statistically significant association with adverse clinicopathologic features such as lymphovascular invasion, multifocality, sessile tumors, and advanced pathologic stage (P < 0.01). On multivariable models, higher pathologic tumor stage, multifocality, and lymph node involvement were associated with RFS, OS, and CSS, but not the overexpression of uPA, uPAR, or PAR-1. In patients with organ-confined disease (≤pT2N0), however, uPA was significantly associated with RFS (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.21-3.43), OS (HR: 1.59, 95% CI:1.08-2.24) and CSS (HR: 2.55, 95% CI:1.44-4.52). uPA improved the predictive accuracy of a standard post-RNU model for all 3 endpoints, in organ-confined disease, by a prognostically significant margin., Conclusions: Overexpression of uPA system components was associated with adverse clinicopathologic characteristics and survival outcomes on the univariable, but not multivariable analyses. uPA expression was an independent predictor of survival outcomes in patients with organ-confined disease. While the clinical value of the uPA system remains limited in this cohort, further studies are needed to identify a marker or constellation of markers of high predictive value to help in counseling and treatment planning of UTUC patients., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Evaluate the safety, feasibility and efficiency of robot-assisted radical prostatectomy (RARP) in kidney transplant recipients, performed in high-volume French referral centres, and describe intra- and postoperative, oncological and functional outcomes., Materials and Methods: A multicentre study was conducted on prospective RARP databases from 5 centres between 2008 and 2017. We retrospectively identified a first group (G1) of transplant patients. The following data were collected: age, body mass index, prostate-specific antigen, ISUP score, TNM stage, stratification according to d'Amico, renal function, renal disease, time between renal transplant and prostate cancer (PCa), operating time, bleeding, pre- and postoperative complications (according to Clavien). Group 1 data were matched with a second group (G2) of nontransplanted PTRA patients., Results: A total of 321 patients were included (G1 N = 39 and G2 N = 282). The median operating time was 180 minutes (interquartile range 125-227) for G1 and 150 minutes (120-180) in G2 (P = 0.0623) and the median bleeding volume was 150 mL (150-400) and 250 mL (175-400), respectively (P = 0.1826). No grafts were damaged by RARP. Postoperative complication rate was significantly higher in G1: 51.2% vs. G2: 8.2% with a majority of minor complications (41%) according to Clavien Dindo (P < 0.001). Pathological assessment was as follows in G1: T2 = 28 (71.8%), T3 = 11 (28.2%), and G2: T2 = 206 (73.3%), T3 = 75 (26.7%) (P = 0.77). Postoperative ISUP scores were mainly grade 1: G1 = 14 (35.9%) vs. 99 (35.2%) in G2 and grade 2: respectively 18 (46.1%) 94 (33.5%). The rate of positive surgical margins was comparable in both groups: 13.2% for transplant patients vs. 18.1% (P = 0.65). Renal function was not significantly different at one year (P = 0.07). The median follow-up was 47.9 months (42.3; 52.5)., Conclusion: RARP is conceivable to treat localized prostate cancer in kidney transplant recipients. This procedure does not appear to have any negative impact on graft renal function and cancer prognosis., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction and Objectives: To evaluate the prognostic role of modified Glasgow prognostic score (mGPS) for the prediction of oncological outcomes in a retrospective large multicenter cohort of upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU)., Materials and Methods: We retrospectively analyzed a multicenter cohort of patients treated with RNU for clinically nonmetastatic UTUC. Multivariable logistic regression analyses were performed to evaluate the ability of mGPS to predict nonorgan confined (NOC) disease and lymph-node involvement (LNI) at RNU. Multivariable Cox-regression models were performed to evaluate the preoperative and postoperative prognostic effect of mGPS on survival outcomes., Results: Overall, 2,492 patients were included in the study. Of these, 1,929 (77%), 530 (21%), and 33 (1%) had a mGPS of 0, 1, and 2, respectively. mGPS was associated with characteristics of tumor aggressiveness and independently predicted LNI and NOC at RNU (both P < 0.05). On univariable and multivariable Cox-regression analyses, higher mGPS was independently associated with recurrence-free, cancer-specific, and overall survival, both in a preoperative and in a postoperative setting. The inclusion of mGPS significantly improved the discrimination of a preoperative model for the prediction of oncologic outcomes compared to standard prognosticators., Conclusions: We found that mGPS is independently associated with clinicopathologic features and survival outcomes after RNU. Future studies should investigate the role of mGPS in a panel of preoperative markers for the prediction of NOC and LNI in UTUC patients, thus possibly improving the selection for perioperative systemic therapy., Competing Interests: Conflicts of interest I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript are the following: Shahrokh Shariat owns or co-owns the following patents: Methods to determine prognosis after therapy for prostate cancer. Granted 2002-09-06. Methods to determine prognosis after therapy for bladder cancer. Granted 2003-06-19. Prognostic methods for patients with prostatic disease. Granted 2004-08-05. Soluble Fas: urinary marker for the detection of bladder transitional cell carcinoma. Granted 2010-07-20. He is advisory board member of Astellas, Cepheid, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanofi, and Wolff. He is speaker for Astellas, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanochemia, Sanofi, and Wolff. The other authors made no disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To validate the predictive and prognostic role of the De Ritis ratio in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy in a large multi-institutional cohort., Materials and Methods: The preoperative De Ritis ratio was assessed in a multi-institutional cohort of 2,492 patients. An altered De Ritis ratio was defined as a ratio >1.35. Logistic regression analyses were performed to assess the association of the De Ritis ratio with advanced disease. The association of the De Ritis ratio with survival outcomes was evaluated using Cox proportional hazards regression models., Results: An altered De Ritis ratio was observed in 985 (41.5%) patients; it was associated with a more advanced pathological features. In a preoperative model, the De Ritis ratio was an independent predictive factor for the presence of lymph node metastasis and muscle-invasive and nonorgan-confined disease (P < 0.05). Compared to patients with a normal De Ritis ratio, those with an altered De Ritis ratio had worse recurrence free (P <0.0001), cancer specific (P = 0.0003), and overall survival (P = 0.0014) in the Kaplan-Meier analyses. In the multivariable analyses that was adjusted for the effects of standard clinicopathologic features, the De Ritis ratio did not retain its independent prognostic value., Conclusions: In UTUC, the preoperative De Ritis ratio is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC. Therefore, it might be useful to incorporate the De Ritis ratio into prognostic tools in selecting appropriate treatment strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors., Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points., Materials and Methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018., Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP., Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC., Materials and Method: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis., Results: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology., Conclusions: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To assess the role of the urokinase plasminogen activator (uPA) system as a prognostic biomarker in patients with nonmuscle invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB) with or without adjuvant intravesical therapy., Material and Methods: We stained TURB tissue from 827 NMIBC patients with uPA, its receptor (uPAR) and its inhibitor (PAI-1). The status of these markers was categorized as normal vs. overexpressed using the cutoffs of 30% for uPA, 50% for uPAR, and 30% for PAI-1. Multivariable Cox regression analyses were performed to evaluate the prognostic value of these markers., Results: uPA was overexpressed in 37.7% of patients, uPAR in 44.7% and PAI-1 in 44.6%. Overexpression of these markers was associated with high tumor grade. Within a median follow-up was 60 months (interquartile range: 22-109), uPA (hazard ratio [HR]: 1.40; P = 0.006), uPAR (HR: 1.70; P < 0.001), PAI-1 (HR: 1.35; P = 0.014), and the combination of all 3 markers (HR: 3.38; P < 0.001) were associated with recurrence-free survival (RFS); uPA (HR: 1.68; P = 0.035) and the combination of all 3 markers (HR: 8.79; P = 0.005) were associated with progression-free survival (PFS). The addition of the uPA system to a base model improved the discrimination by 1.3% for RFS and 2.1% for PFS. In subgroup analyses, uPA (HR: 2.19; P = 0.018) was associated with PFS in T1G3 patients and its addition to a base model improved the discrimination by 2.5%. uPA (HR: 1.44; P = 0.019), uPAR (HR: 1.54; P = 0.006), PAI-1 (HR: 1.46; P = 0.013) and the combination of all 3 markers (HR: 3.48; P < 0.001) were associated with RFS in TaG1-2 patients and their addition to a base model improved the discrimination by 2.1%., Conclusion: uPA, uPAR, and PAI-1 are overexpressed in one-third to half of patients with NMIBC. Their overexpression is an independent prognosticator of RFS and PFS which improved the predictive accuracy of current clinicopathological characteristics. Biomarkers that capture the biological and clinical behavior of individual tumors may help personalize clinical decision-making in patients with NMIBC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess the oncologic impact of adjuvant endocavitary instillation after kidney-sparing surgery (KSS) in the treatment of upper tract urothelial carcinoma (UTUC)., Methods: A meta-analysis of the available literature was performed using PUBMED and MEDLINE on June 2018. No time or language restrictions were applied. All included participants were substratified into 2 groups: Ta/T1 UTUC and upper tract (UT) carcinoma in situ. Subjects with higher stage disease, involvement of the bladder, or urethra were excluded. Predefined endpoints of interest were rates of cytology response, UT recurrence, UT progression, cancer-specific survival, and overall survival., Results: Overall, 27 eligible reports for a total of 438 patients were identified and 18 studies included for quantitative analyses. All included reports were nonrandomized observational case series. Among studies that reported on UT recurrence, 154 (35%) patients developed UT recurrence during a median follow-up of 30 months. The overall pooled estimates for adjuvant instillations in Ta-T1 patients were 40% for UT recurrence, 94% for cancer-specific survival, and 71% for OS. Subanalyses stratified by regimen used and instillation approach did not show any significant differences. In patients with UT carcinoma in situ treated with BCG, the pooled estimates for cytology response, UT recurrence, and progression were 84%, 34%, and 16%, respectively. Similarly, comparison between instillation approaches did not show any significant differences., Conclusions: In this meta-analysis of presumed nonmuscle invasive patients treated with kidney-sparing surgery, endocavitary instillations for noninvasive UTUC, did not reveal any differences between the regimens and instillations approaches. Patients with Ta-T1 UTUC had an UT recurrence rate comparable to that reported in the literature for nontreated patients. To date, the efficacy of endocavitary instillations in UTUC remains to be demonstrated. Upcoming novel drugs promise to change this paradigm., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The use of robotic-assisted radical cystectomy (RARC) is becoming more widespread. While its safety is accepted, its oncological efficacy as compared to the current standard, open radical cystectomy (ORC), remains debatable., Materials and Methods: The aim of this study is to compare the rates of positive soft tissue surgical margins (STSM), between patients treated with RARC or ORC, using a large contemporaneous collaborative database. We included 2,536 patients with urothelial carcinoma of the bladder treated at 26 institutions. A propensity-score matching 1:1 was performed with 3 ORC patients matched to 1 RARC patient. The final cohort included 1,614 patients. Uni- and multivariable logistic regression analyses tested the impact of surgical technique on STSM status, before and after propensity-score matching., Results: Overall, 870 (34%) patients underwent RARC and 1,666 (66%) ORC. The overall STSM rate was 11%; 10% in the ORC group and 13% in the RARC group. Within the propensity-score-matched cohort, the positive STSM rate were 14% and 13% in the ORC and RARC group, respectively (P = 0.1). In multivariable analysis, after propensity match RARC approach was not associated with the risk of a positive STSM (P = 0.1). These results were confirmed in the subgroup of patients with pathologic non-organ-confined or organ-confined diseases., Conclusions: While treatment with RARC is associated with a higher absolute rate of STSM, the difference did not remain after adjustment for the effects of other established prognostic factors. Results from ongoing trials are awaited to assess the validity of these findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Serum cholinesterase (ChE) a serine hydrolase that catalyses the hydrolysis of esters of choline, is involved in cellular proliferation and differentiation, therefore affecting carcinogenesis. The aim of this study was to understand the prognostic role of preoperative serum ChE in patients with radiation-recurrent prostate cancer (CaP) treated with salvage radical prostatectomy (SRP)., Material and Methods: This retrospective study included 214 patients with radiation-recurrent CaP treated with SRP from January 2007 to December 2015 at 5 academic centers. Patients were considered with abnormal/decreased ChE levels if <5 kU/l. Biochemical recurrence-free and metastases-free (MFS) survival analyses were performed., Results: Median serum ChE level was 6.9 (interquartile range) 6-7.7) kU/l. Serum ChE level (<5 kU/l) was decreased in 25 (11.7%) patients. Decreased serum ChE level was associated with lower body mass index (P = 0.006) and metastasis to lymph nodes (P = 0.004). In multivariable analysis, continuous ChE was an independent predictor of MFS (hazard ratio [HR] 0.48, confidence interval [CI] 0.33-0.71, P < 0.001), overall survival (HR 0.68, CI 0.48-0.96, P = 0.03) and cancer-specific survival (HR 0.41, CI 0.2-0.84, P = 0.01). Serum ChE improved the C-index (by 2.54%) to 87.8% for prediction of overall survival and (by 3%) to 92% for prediction of MFS., Conclusion: Preoperative serum ChE is associated with the development of metastasis in patients with radiation-recurrent CaP who underwent SRP. The biological underpinning of this association with the biological and clinical aggressiveness of CaP needs to be further elucidated., (Copyright © 2018. Published by Elsevier Inc.)

Background: Reliable prognosticators for T1 bladder cancer (T1BC) are urgently needed., Objective: To compare the prognostic value of 2 substage systems for T1BC in patients treated by transurethral resection (TUR) and adjuvant bacillus Calmette-Guérin therapy., Design, Setting, and Participants: The slides of 601 primary T1BCs from four institutes were reviewed by 2 uropathologists and substaged according to 2 classifications: metric substage according to T1 microinvasive (T1m-lamina propria invasion <0.5mm) and T1 extensive invasive (pT1e-invasion ≥ 0.5mm), and according to invasion of the muscularis mucosae (MM) (T1a-invasion above or into MM/T1b)., Outcome Measurements and Statistical Analysis: Multivariable analyses for progression-free (PFS) and cancer-specific survival (CSS) were performed including substage, size, multiplicity, carcinoma in situ, sex, age, WHO-grade 1973, and WHO-grade 2004 as variables., Results: Median follow-up was 5.9 years (interquartile range: 3.3-9.0). Progression to T2BC was observed in 148 (25%) patients and 94 (16%) died of BC. The MM was not present at the invasion front in 135 (22%) of tumors. Slides were substaged as follows: 213 T1m and 388 T1e and 281 T1a and 320 T1b. On multivariable analysis, T1m/e substage and WHO 1973 grade were the strongest prognosticators for PFS (hazard ratio [HR] = 3.8 and HR = 1.8) and CSS (HR = 2.7 and HR = 2.6), respectively. Other prognostic factors for CSS were age (HR = 1.03), and tumor size (HR = 1.8). Substage according to MM-invasion was not significant. Our study was limited by its retrospective design and that standard re-TUR was not performed if TUR was macroscopically complete and muscularis propria was present in resected specimens., Conclusions: Metric substaging of T1BC was possible in all cases of 601 T1BC patients and it was a strong independent prognosticator of both PFS and CSS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To improve current prognostic models for the selection of patients with T1G3 urothelial bladder cancer who are more likely to fail intravesical therapy and progress to muscle-invasive bladder cancer (MIBC)., Materials and Methods: We performed a retrospective analysis of 1,289 patients with pT1G3 urothelial bladder cancer who were treated with transurethral resection of the bladder (TURB) and adjuvant intravesical bacillus-Calmette-Guérin (BCG). Random-split sample data and competing-risk regression were used to identify the independent impact of lymphovascular invasion (LVI) and variant histology (VH) on progression to MIBC. We developed a nomogram for predicting patient-specific probability of disease progression at 2 and 5 years after TURB. Decision curve analysis (DCA) was performed to evaluate the clinical benefit associated with the use of our nomogram., Results: In the development cohort, within a median follow-up of 51.6 months (IQR: 19.3-92.5), disease progression occurred in 89 patients (13.8%). A total of 84 (13%) patients were found to have VH and 57 (8.8%) with LVI at TURB. Both factors were independently associated with disease progression on multivariable competing-risk analysis (HR: 4.4; 95% CI: 2.8-6.9; P<0.001 and HR: 3.5; 95% CI: 2.1-5.8; P<0.001, respectively). DCA showed superior net benefits for the nomogram within a threshold probability of progression between 5% and 55%. Limitations are inherent to the retrospective design., Conclusions: We demonstrated the clinical value of the integration of LVI and VH in a prognostic model for the prediction of MIBC. Indeed, our tool provides superior individualized risk estimation of progression facilitating decision-making regarding early RC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Overexpression of Caveolin-1 has been associated with cancer growth, migration, and metastases in several malignancies, but only few data are available on its role in bladder cancer (BCa). The aim of this study is to validate Caveolin-1 as a prognosticator of recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in a large cohort of patients treated with radical cystectomy (RC) for BCa., Methods: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray from 424 patients treated with RC for UCB at a single institution. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positively. Univariable and multivariable Cox proportional hazards regression models were used to assess the association of Caveolin-1 expression with RFS, OS, and CSS., Results: Overexpression of Caveolin-1 was observed in 116 (27.4%) patients and was associated with lymph node metastasis (P = 0.003). Median follow-up for patients alive at last follow-up was 129 months (interquartile range [IQR]: 82-178). Patients with overexpression of Caveolin-1 had significant worse RFS, OS, and CSS compared to those with normal expression (log-rank test, P = 0.008, P = 0.001, and P = 0.005, respectively). At multivariable analyses that adjusted for the effects of standard clinicopathologic features, Caveolin-1 remained associated with OS (hazard ratio = 1.47, P = 0.002) and CSS (hazard ratio = 1.42, P = 0.03). Conversely, no association with RFS was found (P = 0.1). Addition of Caveolin-1 in a model for prediction of survival did not improve the accuracy of the prognostic model. Actually, C-index did not differ among models with or without Caveolin-1 (0.72 for a model predicting RFS, 0.65 for OS, and 0.71 for CSS)., Conclusions: Caveolin-1 is overexpressed in one-third of patients with BCa treated with RC. Overexpression of Caveolin-1 is significantly associated with OS and CSS, but not with RFS, in patients with BCa treated with RC. However, it is not clinically useful as it does not improve upon the predictive accuracy of survival achieved by pathologic variables alone., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of preoperative anemia (PA) on oncological outcomes in a multicenter cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB) and adjuvant intravesical therapies. We hypothesize that PA represents a marker of disease aggressiveness and could be used to improve the discrimination of prognostic tools for the prediction of disease recurrence and progression., Methods: This multicenter retrospective study included 1,117 patients from 4 different centers. The presence of PA was assessed according to the World Health Organization classification as a preoperative hemoglobin level of≤13g/dl in men and≤12g/dl in women. PA evaluation was done at each institution, generally 1 to 3 days before surgery. Multivariable Cox regression models were performed to evaluate the prognostic effect of PA on survival outcomes., Results: Overall, 381 (34%) patients with NMIBC treated with TURB, had PA. Median follow-up for patients alive at last follow-up was 62.7 months (interquartile range: 25-110.7). On multivariable Cox regression analyses that accounted for the effect of standard clinicopathologic prognosticators, PA was independently associated with recurrence-free survival (P = 0.045) and progression-free survival (P = 0.01). Adding PA to a model for the prediction of disease recurrence and progression improved the discrimination of the prognostic models marginally from 69.8% to 70.3% and from 71.6% to 73.1%, respectively., Conclusions: PA was found in more than one-third of patients with NMIBC treated with TURB. PA was associated with poor oncological outcomes and was an independent predictor of intravesical disease recurrence and progression. However, the additional prognostic information provided by PA remains limited., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To externally validate our previously developed pathological nodal staging model (pNSS) that allows quantification of the likelihood that a patient with pathologic node-negative status has, indeed, no lymph node metastasis (LNM)., Patients and Methods: We analyzed data from 2,768 patients treated with radical nephroureterectomy (RNU) and lymph node dissection (LND) using the Surveillance, Epidemiology, and End Results database from 1988 to 2010. We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a new pNSS. Then, we compared these findings with those of the initial cohort., Results: The mean and median numbers of lymph node (LN) removed were 5 and 2, respectively (interquartile range = 5) in the validation cohort, though 66.5% of the patients (n = 1814) were pN0. Similar to the development cohort, the probability of missing a LNM decreased as the number of nodes examined increased in the validation cohort. If only a single node was examined, 35% of patients would be misclassified as pN0 while harboring LNM. Even when 5 nodes were examined, 8% would be misclassified. The probability of having a positive node increased with advancing pathological T stage in both the cohorts. Patients with pT0-Ta-Tis-T1 disease in both cohorts would have more than a 95% chance of a correct pathologic nodal staging with 2 examined nodes. However, if a patient has pT3-T4 disease, more than 12 examined LNs are needed to reach 95% accuracy., Conclusions: We confirmed that the number of examined nodes needed for adequate staging depends on pT category. We externally validated our previous pNSS in a population-based database, which could help in the clinical decision-making regarding adjuvant chemotherapy administration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with bladder cancer (BCa) and to assess its association with oncological outcomes., Methods: This retrospective single-center study included 354 patients with BCa treated with radical cystectomy (RC). HER2 status was assessed with immunohistochemistry and scored according to HercepTest. Conditional survival and competing risk regression were performed to assess the association between HER2 expression and survival outcomes., Results: HER2 was overexpressed in 36% of patients. HER2 overexpression was associated with features of tumor aggressiveness such as lymph-node metastases (P = 0.002). At a median follow-up of 123 months (interquartile range: 79-180), 160 patients (45%) experienced disease recurrence, 263 patients (74%) died and 157 (44%) died of cancer. On multivariable analyses, HER2 overexpression was not significantly associated with any oncological outcomes. Adding HER2 status to a model for the prediction of survival outcomes did not change the accuracy of the model for any of the outcomes. Interestingly, HER2 status significantly affected late disease recurrence (P = 0.05 for conditional survival at 24 months)., Conclusions: More than one third of RC patients overexpress HER2 in their tumors. HER2 overexpression was associated with features of biological and clinical aggressiveness. HER2 did not add prognostic significance to the standard established predictors of survival outcomes after RC. However, due to the high overexpression rate, it could represent a target for therapy in select advanced BCa tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein (CRP) are markers of systemic inflammatory response, which have been associated with the prognosis of multiple malignancies, but their relationships with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) have not been well studied yet., Patients and Methods: We retrospectively reviewed the medical records of 1,117 patients with NMIBC who underwent a transurethral resection of the bladder. Univariable and multivariable competing risk regression models were used to assess the association of preoperative NLR and CRP with disease recurrence and progression to muscle-invasive disease. The median follow-up was 64 months., Results: In total, 360 patients (32.2%) had a high NLR (≥2.5) and 145 (13.0%) had a high CRP (≥5mg/l). On multivariable analyses, a high NLR was associated with both disease recurrence (subhazard ratio [SHR] = 1.27, P = 0.013) and progression (SHR = 1.72, P = 0.007), and high CRP was associated with disease progression (SHR = 1.72, P = 0.031). Adding NLR and CRP to the multivariable model predicting disease progression lead to a relevant change in discrimination (+2.0%). In a subgroup analysis of 300 patients treated with bacillus Calmette-Guerin, both high NLR and high CRP were associated with disease progression (SHR = 2.80, P = 0.026 and SHR = 3.51, P = 0.021, respectively), and NLR was associated with disease recurrence (SHR = 1.46, P = 0.046). There was also an increase in the discrimination of the model predicting progression after bacillus Calmette-Guerin following the inclusion of both markers (+2.4%)., Conclusion: In patients with NMIBC, markers of systemic inflammation response are associated with disease recurrence and progression. The inclusion of such markers in prognostic models does enhance their accuracy., (Copyright © 2016. Published by Elsevier Inc.)

Objective: Several small single-center studies have reported conflicting results on the prognostic value of survivin expression in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy. We attempted to validate the prognostic utility of survivin using a large multi-institutional cohort., Material and Methods: Survivin expression was evaluated by immunohistochemistry in tumor tissue from 732 patients with unilateral, sporadic UTUC treated with radical nephroureterectomy between 1990 and 2008 at 7 centers. Survivin expression was considered altered when at least 10% of the tumor cells stained positive. Associations of altered survivin expression with recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Cox proportional hazards regression models., Results: Altered survivin expression was observed in 288 (39.3%) tumors and was associated with more advanced pathological tumor stages (P<0.001), lymph node metastases (P<0.001), lymphovascular invasion (P<0.001), tumor necrosis (P = 0.027), and tumor architecture (P<0.001). Median follow-up was 35 (16-64) months. There were 191 (25.4%) patients who experienced disease recurrence, and 165 patients (21.9%) died of the disease. In the univariable analysis, altered survivin expression was significantly associated with worse RFS and CSS (each P<0.001); however, altered survivin expression did not achieve independent predictive status on multivariable models (P = 0.24 and P = 0.53). Similarly, survivin was not independently associated with outcomes in subgroup analyses, including patients with high-grade tumors., Conclusions: In UTUC, altered survivin expression is associated with worse clinicopathological features and worse RFS and CSS. However, it does not appear to be independently associated with cancer outcomes when considering standard prognostic factors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Controversy exists regarding the propensity of hypogonadism and metabolic disorders to promote the development of high-risk prostate cancer (PCa). Our aim was to prospectively test whether preoperative circulating testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with aggressive pathological features after radical prostatectomy (RP)., Material and Methods: Overall, 354 patients undergoing robot-assisted RP at our academic institution, between 2010 and 2013, to treat clinically localized PCa were included in this prospective study. Pelvic lymphadenectomy was performed in 116 (32.8%) patients and confirmed the absence of nodal metastases in all of them. Cardiovascular risk factors and body-mass index (BMI) were used to define MetS and obesity, respectively. Total testosterone (TT) levels were assessed using an immunoassay method, whereas bioavailable testosterone (BT) and free testosterone (FT) levels were estimated using Vermeulen׳s formula. Multivariate logistic regression analyses assessed independent predictors for postoperative aggressive pathological features (i.e., a pathological Gleason score [GS] ≥ 7, extracapsular extension [ECE], seminal vesicle invasion [SVI], and positive surgical margins [PSM]) and GS upgrading., Results: Low TT, BT, and FT levels were found in 54 (15.2%), 70 (19.8%), and 62 (17.5%) patients, respectively. Median BMI was 26.3 kg/m(2) (range: 17.4-43.9), and prevalence of MetS was 18.9%. Significantly higher rates of pathological GS ≥ 7 were observed in groups with a low TT level (46.3% vs. 33.3%; P = 0.01), low BT level (44.3% vs. 33.1%; P<0.001), and low FT level (46.8% vs. 32.9%; P = 0.001). Multivariate analyses demonstrated that only low BT and FT levels were independent predictors of pathological GS ≥ 7 (odds ratio [OR] = 1.76; P<0.001 and OR = 1.39; P<0.001, respectively) and GS upgrading (OR = 2.82; P<0.001 and OR = 1.71; P<0.001, respectively), but there was no significant correlation between low circulating testosterone levels and ECE, SVI, or PSM. Furthermore, BMI (OR = 1.28; P = 0.04) and MetS (OR = 1.19; P = 0.01) were only correlated with PSM., Conclusion: Hypogonadism, obesity, and MetS were not independent predictors of pathological GS ≥ 7, ECE, or SVI after RP. Our data suggest that only low BT and FT levels, which might logically result in an active androgen-depleted environment, were linked with high-grade PCa., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To assess the prognostic significance of lymphovascular invasion (LVI), maximum tumor diameter (MTD), high-grade prostatic intraepithelial neoplasia, perineural invasion, and length of positive surgical margins after robot-assisted radical prostatectomy (RARP)., Methods: A single-institution prospective analysis of all patients who underwent RARP for localized prostate cancer was performed between January 2005 and June 2013. The primary end point was biochemical recurrence-free survival (BRFS). BRFS was estimated using the Kaplan-Meier method and compared to that from the log-rank test. Cox׳s proportional hazards regression univariate and multivariate analyses were performed to define the prognostic factors., Results: Overall, 742 men were included. After a median follow-up of 31.4 months, biochemical recurrence occurred in 80 patients (10.8%). BRFS was 93%, 87%, and 80.7% at 1, 3, and 5 years, respectively. Progression to local recurrence occurred in 49 patients (6.6%). During the follow-up period, 3 patients experienced progression to metastatic disease and were treated with hormonotherapy. No patient died of disease during the study period. In multivariate analyses, Gleason score was the strongest predictor of BRFS (hazard ratio [HR] = 3.4; P<0.001). There were 3 other predictive factors of BRFS were LVI (HR = 7.64; P = 0.005), MTD (HR = 4.04; P =0.009), and margin length ≥ 3 mm (HR = 1.25; P = 0.04)., Conclusion: In the era of serum prostate-specific antigen testing maturity in conjunction with a single approach to extirpation of the prostate gland by RARP, LVI, MTD, and positive surgical margins ≥ 3 mm are prognostic factors associated with BRFS after RARP. Consideration could be given to incorporate them in the pathology report of the radical prostatectomy specimens and they could assist physicians in clinical decision making., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5., Material and Methods: We retrospectively reviewed the data from 4,146 patients with localized (pT2-3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model., Results: Of the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features (P<0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group (P<0.001)., Conclusions: Knowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: ABO blood type is an inherited characteristic that has been associated with the prognosis of several malignancies, but there is little evidence in urothelial carcinoma of the bladder (UCB). The purpose of this study was to evaluate the effect of ABO blood type on mortality in patients with UCB treated with radical cystectomy (RC)., Methods: Multi-institutional data from 7,906 patients with UCB treated with RC between 1979 and 2012 were retrospectively analyzed. The effect of ABO blood type on UCB-related mortality was evaluated with univariable and multivariable competing-risks regression models., Results: ABO blood type was O in 3,728 (47%), A in 2,748 (35%), B in 888 (11%), and AB in 532 (7%) patients. Blood type B was associated with a greater likelihood of lymphovascular invasion (P = 0.010) and positive soft tissue margins (P = 0.008). The median follow-up was 41 months. The 5-year cumulative UCB-related mortality rates for blood type O, A, B, and AB were 29.5%, 30.5%, 33.2%, and 25.8%, respectively. In univariable competing-risks regression, patients with blood type B had worse UCB-related mortality than those with blood type O (P = 0.026) and AB (P = 0.020). In multivariable analysis, however, blood type lost its statistical significance., Conclusions: Among patients treated with RC, ABO blood type is associated with a statistically significant but clinically insignificant difference in UCB-related mortality. This association was not present in multivariable analysis. Our data therefore suggest no relevant association of ABO blood type with UCB-related prognosis., (© 2013 Published by Elsevier Inc.)

Objective: The objective of the study was to evaluate the effect of a history of bladder cancer (BC) or synchronous BC on the prognosis and survival of patients who have undergone radical nephroureterectomy (RNU)., Methods and Materials: Using a multi-institutional, retrospective database, we identified 662 patients with upper urinary tract urothelial carcinoma (UUT-UC) treated by radical nephroureterectomy, between 1995 and 2010. We analyzed clinicopathologic characteristics and outcomes according to the history of BC or concomitant BC or both, at the time of diagnosis. BC was evaluated as a prognostic factor for bladder recurrence and survival., Results: Overall, 83 (12.5%) patients had previous BC, 62 (9.4%) exhibited concomitant BC, and 75 (11.3%) presented with both previous and current BC. A history of BC was less seen in women and nonsmokers (P<0.0001 and P = 0.013, respectively). The patients with associated BC had more tumors located in the ureter (P<0.0001), as well as more multiple locations in the upper tract (P<0.0001). The tumors without concomitant BC were more likely to be associated with locally advanced stages (P = 0.024). At a median follow-up time of 37.3 months, 31.4% of patients experienced BC recurrence and 2.9% developed contralateral upper tract tumor. Using multivariate analyses, the previous or synchronous BC (P = 0.01) and positive surgical margins (P = 0.03) are independent prognostic factors for BC recurrence. The metastasis-free survival and cancer-specific survival rates did not significantly differ according to the associated BC status., Conclusions: In patients without previous or concomitant BC, the upper tract tumors are more frequently localized in the renal pelvis and are associated with a more invasive status at the time of diagnosis. Nevertheless, the presence of UUT-UC without previous or synchronous BC did not significantly affect the survival rates after nephroureterectomy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To determine if the number of lymph nodes (LNs) removed is an independent predictor of biochemical recurrence (BCR) in patients without LN metastases undergoing radical prostatectomy (RP)., Material and Methods: Retrospective analysis of 7,310 patients treated at 7 centers with RP and pelvic LN dissection for clinically localized prostate cancer between 2000 and 2011. Patients with LN metastases (n = 398) and other reasons (stated later in the article) (n = 372) were excluded, which left 6,540 patients for the final analyses., Results: Overall, median biopsy and RP Gleason score were both 7; median prostate specific antigen level was 6 ng/ml (interquartile range [IQR]: 5); and median number of LNs removed was 6 (IQR: 8). A total of 3,698 (57%), 2,064 (32%), and 508 (8%) patients had ≥ 6, ≥ 10, and ≥ 20 LNs removed, respectively. Patients with more LNs removed were older, had a higher prostate specific antigen level, had higher clinical and pathologic T stage, and had higher RP Gleason score (all P<0.002). Within a median follow-up of 21 (IQR: 16) months, more LNs removed was associated with an increased risk of BCR (continuous: P = 0.021; categorical: P = 0.014). In multivariable analyses that adjusted for the effects of standard clinicopathologic factors, none of the nodal stratifications predicted BCR., Conclusions: The number of LNs did not have any prognostic significance in our contemporary cohort of patients with LN-negative prostate cancer. This suggests that the risk of missed clinically significant micrometastasis may be minimal in patients currently treated with RP and having a lower LN yield., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To prospectively compare surgical and pathologic outcomes obtained by elective robot-assisted (RAPN) or open partial nephrectomy (OPN) for small renal cell carcinoma (RCC)., Materials and Methods: Between 2008 and 2010, after protocol design and patient consent, we prospectively collected clinical data for 100 patients who concurrently underwent either OPN (58) or RAPN (42) by an individual experienced surgeon. Clinical data included age, BMI, and past medical history. Operative data included operative time, warm ischemia time (WIT), and estimated blood loss (EBL). Postoperative outcomes included hospital stay (LOS), creatinine variation, Clavien complications, pathologic results, and survival. We stratified the complexity of the renal tumor using the R.E.N.A.L Nephrometry score., Results: Of note, RAPN was superior to OPN in terms of EBL (median 143 mL vs. 415; P < 0.001) and LOS (median 3.8 days vs. 6.8; P < 0.0001). The median WIT for the RAPN group was 17.5 minutes (vs. 17.1 OPN; P = 0.3)) and the mean strict operative time was 134.8 minutes (vs. 128.4 OPN; P = 0.097). Regarding immediate, early, and short-term complications, variation of creatinine levels, and pathologic margins, the rates were equivalent for both groups (P > 0.05). According to the R.E.N.A.L nephrometry scores, both groups (RAPN/OPN) had similar rates (%) of low (81/72.4) and intermediate (19/20.7) complexity tumors, though there were 4 high complexity tumors in OPN group (vs. 0; P = 0.03)., Conclusion: We found that RAPN is superior to the reference standard (OPN) surgical treatment of small RCCs in terms of blood loss and length of hospital stay with equivalent complications, warm ischemia time, and effect on renal function. Larger randomized trials with longer follow-up will give us further information and insight into the oncologic equivalence., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate the role of pelvic phased array MRI in staging prostate cancer (CaP)., Materials and Methods: We prospectively collected data over 12 months on CaP patients who underwent preoperative MR imaging with a pelvic phased array before radical prostatectomy. MR images were analyzed prospectively by 2 radiologists. MR imaging findings were then correlated with pathologic findings., Results: Overall, 101 patients were included with a mean PSA level of 8 (range 1.8-30). Reader 1 (AUC 0.895, 95% CI 0.791-0.999) had a higher performance than reader 2 (AUC 0.687, 95% CI, 0.555-0.819) and than DRE (AUC 0.728, 95% CI, 0.599-0.857) in discriminating T2 from T3 CaP (P = 0.01). The κ-index of inter-observer agreement was 0.56. A model that combines MRI findings, DRE, PSA, and Gleason score was the most competitive for staging (AUC 0.895, 95% CI, 0.791-0.999). For the multivariate analysis, 3 criteria were significantly associated with extracapsular extension: asymmetry of the neuro-vascular bundles (P = 0.001), asymmetric enhancement of neurovascular bundles (P = 0.02), and bulging of the capsule (P = 0.0003)., Conclusion: Pelvic phased array MRI presented satisfying results in its ability to adequately stage CaP and notably in detecting the extracapsular extension of tumors. It is likely to provide reliable information but rather in the hands of an experienced radiologist., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Urothelial cell carcinoma of the upper urinary tract (UUT-UCC) is a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. This review highlights the main chemotherapy regimens available for UUT-UCCs based on the recent literature., Materials and Methods: Data on urothelial malignancies and UUT-UCCs management in the literature were searched using MEDLINE and by matching the following key words: urinary tract cancer; urothelial carcinomas; upper urinary tract; carcinoma; transitional cell; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; neoadjuvant treatment; recurrence; risk factors; and survival., Results: No evidence level 1 information from prospective randomized trials was available. Because of its many similarities with bladder urothelial carcinomas, chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. Most teams have proposed a neoadjuvant or an adjuvant treatment based either on the combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) or on gemcitabine/cisplatin (GC). These regimens have been shown to prolong survival moderately. All recent studies have included limited numbers of patients and have reported poor patient outcomes after both neoadjuvant and adjuvant chemotherapy. Regarding metastatic UUT-UCCs, vinflunine has demonstrated moderate activity in these patients with a manageable toxicity. Interestingly, specific molecular markers [microsatellite instability (MSI), E-cadherin, HIF-1α, and RNA levels of the telomerase gene] can provide useful information that can help diagnose and determine patient prognosis in patients with UUT-UCC., Conclusion: Chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. However, there is no strong evidence that chemotherapy is effective due to the rarity of the disease and the lack of data in the current literature. Thus, physicians must take into account the specific clinical characteristics of each individual patient with regard to renal function, medical comorbidities, tumor location, grade, and stage, and molecular marker status when determining the optimal treatment regimen for their patients. The ongoing identification of the oncologic mechanisms of this type of cancer might pave the way for the development of specific treatments that are targeted to the characteristics of each patient's tumor in the future., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To analyze clinical characteristics and pathologic findings in patients eligible for active surveillance (AS) who underwent radical prostatectomy (RP)., Materials and Methods: We collected data from 495 patients who underwent RP during an 8-year period. We have then selected those who would have been eligible for AS according to 2 different sets of published criteria. Group 1 used broader criteria: clinical stage ≤ T2b, Gleason score of seven or less and PSA ≤ 15 ng/ml. Group 2 used more restrictive criteria: age < 75 years, PSA < 10 ng/ml, clinical stage T1c or T2a, Gleason score of 6 or less, at least 10 biopsies available and a tumor length of less than 3 mm in 2 biopsy cores., Results: Overall, 207 patients (41.8%) were included in group 1 and 43 (8.7%) in group 2. The median follow-up was 31 (3-108) and 32 (3-84) months in groups 1 and 2, respectively. We recorded 132 cases (63.8%) of pT2c in group 1 and 31 in group 2 (72.1%). Extracapsular extension was noted in 37 (17.9%) and 2 (4.7%) specimens from groups 1 and 2, respectively. In groups 1 and 2, a biochemical failure occurred in 47 patients (22.7%) and 6 (14%), respectively. The Gleason score at biopsy was underestimated in 54 (26%) and 9 (21%) of patients in groups 1 and 2, respectively., Conclusion: Overall, 21% to 26% of patients eligible for AS had upgraded Gleason scores at prostatectomy and actually had a more significant disease with a potentially aggressive behavior. Therefore, based on criteria, certain tumors currently selected for AS may be significant and may require radical treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To investigate whether overexpression of p53, MIB-1, and Aurora-A on protein level played a role in the relapse of urothelial carcinomas of the upper urinary tract (UC-UUT)., Materials and Methods: The following data from the files of 42 patients treated for UC-UUT were collated: age, prior history of cancer, tumor stage and grade, and disease progression. Immunohistochemistry (IHC) for p53, MIB-1, and Aurora-A was performed on tissue microarray sections from tumor tissue., Results: Patients aged 46 to 100 years (mean 70.6 years). Overall, 23 (54%) patients died from progression of UT-UCC. The surgical stage was significantly associated with MIB-1 and Aurora-A overexpression (P = 0.004 for each). Univariate analysis showed that relapse was significantly associated with ureteral localization (P = 0.02), the presence of vascular invasion (VI) (P = 0.003), high grade (P = 0.04), high stage UT-UCCs (P = 0.02), and p53 (P = 0.01), Aurora-A (P = 0.01), and MIB-1 overexpression (P = 0.02). In multivariate analysis, relapse was associated with high grade (P = 0.04), high stage (P = 0.04), VI (P < 0.0001, respectively), and p53 (P = 0.04) and Aurora-A (P = 0.02) overexpression but not with MIB-1 overexpression (P = 0.06). In addition, expressions of p53, MIB-1, and Aurora-A were significantly associated with presence of VI (P = 0.008, P = 0.001, and P = 0.003, respectively)., Conclusion: Aurora-A and p53 are important factors in UC-UUT development and might be useful as independent factors for predicting clinical outcome and presence of VI. Aurora-A seems to influence the development of VI and tumor aggressiveness via a mechanism not clearly elucidated yet., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8., Materials and Methods: We performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery., Results: Overall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9-31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤ 7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%., Conclusion: RP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To highlight the main risk factors for metachronous bladder recurrence after treatment of an upper urinary tract urothelial cell carcinomas (UUT-UCCs) based on the recent literature., Materials and Methods: Data on urothelial malignancies after UUT-UCCs management in the literature were searched using MEDLINE and by matching the following key words: urinary tract cancer; bladder carcinomas, urothelial carcinomas, upper urinary tract, renal pelvis, ureter prognosis, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, cystectomy, nephroureterectomy, minimally invasive surgery, recurrence, and survival., Results: No evidence level 1 information from prospective randomized trials was available. A range of 15% to 50% of patients with a UUT-UCC will subsequently develop a metachronous bladder UCC. Intraluminal tumor seeding and pan-urothelial field change effect have both been proposed to explain intravesical recurrences. In most cases, bladder cancer arises in the first 2 years after UUT-UCC management. However the risk is lifelong and repeat episodes are common. The identification of variables that allow accurate risk stratification of UUT-UCC patients with regards to future bladder relapse is disappointing. No factors have been identified to date that can reliably predict bladder recurrences. A history of bladder cancer prior to UUT-UCC management and upper tract tumor multifocality are the only frequently reported clinical risk factors among current literature., Conclusion: Prior histories of bladder cancer and upper tract tumor multifocality are the most frequently reported risk factors for bladder tumors following UUT-UCCs. Surveillance regimen is based on cystoscopy and on urinary cytology for at least 5 years., (Copyright © 2011 Elsevier Inc. All rights reserved.)