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Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participants: This was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

BACKGROUND: Head-to-head comparisons between ileal conduit (IC) and orthotopic neobladder (ONB) in terms of peri- and postoperative outcomes and complications, in the specific setting of robot-assisted radical cystectomy (RARC), are not available. OBJECTIVE: To address the impact of the type of urinary diversion (UD, IC vs ONB) on RARC morbidity, as well as operative time (OT), length of stay (LOS), and readmissions. DESIGN, SETTING, AND PARTICIPANTS: Urothelial bladder cancer patients treated with RARC at nine high-volume European institutions between 2008 and 2020 were identified. INTERVENTION: RARC with either IC or ONB. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intra- and postoperative complications were collected and reported according to the Intraoperative Complications Assessment and Reporting with Universal Standards recommendations and European Association of Urology guidelines, respectively. Multivariable logistic regression models tested the impact of UD on outcomes, after adjustment for clustering at single hospital level. RESULTS AND LIMITATIONS: Overall, 555 nonmetastatic RARC patients were identified. In 280 (51%) and 275 (49%) patients, an IC and an ONB were performed, respectively. Eighteen intraoperative complications were recorded. The rates of intraoperative complications were 4% in IC patients and 3% in ONB patients (p = 0.4). The median LOS and readmission rates were 10 versus 12 d (p

To determine the oncological impact and adverse events of performing simultaneous transurethral resection of bladder tumour (TURB) and transurethral resection of the prostate (TURP), as evidence on the outcomes of simultaneous TURB for bladder cancer and TURP for obstructive benign prostatic hyperplasia is limited and contradictory.Patients from 12 European hospitals treated with either TURB alone or simultaneous TURB and TURP (TURB+TURP) were retrospectively analysed. A propensity score matching (PSM) 1:1 was performed with patients from the TURB+TURP group matched to TURB-alone patients. Associations between surgery approach with recurrence-free (RFS) and progression-free (PFS) survivals were assessed in Cox regression models before and after PSM. We performed a subgroup analysis in patients with risk factors for recurrence (multifocality and/or tumour size3 cm).A total of 762 men were included, among whom, 76% (581) underwent a TURB alone and 24% (181) a TURB+TURP. There was no difference in terms of tumour characteristics between the groups. We observed comparable length of stay as well as complication rates including major complications (Clavien-Dindo Grade ≥III) for the TURB-alone vs TURB+TURP groups, while the latest led to longer operative time (P 0.001). During a median follow-up of 44 months, there were more recurrences in the TURB-alone (47%) compared to the TURB+TURP group (28%; P 0.001). Interestingly, there were more recurrences at the bladder neck/prostatic fossa in the TURB-alone group (55% vs 3%, P 0.001). TURB+TURP procedures were associated with improved RFS (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.29-0.53; P 0.001), but not PFS (HR 1.63, 95% CI 0.90-2.98; P = 0.11). Within the PSM cohort of 254 patients, the simultaneous TURB+TURP was still associated with improved RFS (HR 0.33, 95% CI 0.22-0.49; P 0.001). This was also true in the subgroup of 380 patients with recurrence risk factors (HR 0.41, 95% CI 0.28-0.62; P 0.001).In our contemporary cohort, simultaneous TURB and TURP seems to be an oncologically safe option that may, even, improve RFS by potentially preventing disease recurrence at the bladder neck and in the prostatic fossa.

Contains fulltext : 244217.pdf (Publisher’s version ) (Open Access) CONTEXT: During the past decade, several urinary biomarker tests (UBTs) for bladder cancer have been developed and made commercially available. However, none of these is recommended by international guidelines so far. OBJECTIVE: To assess the diagnostic estimates of novel commercially available UBTs for diagnosis and surveillance of non-muscle-invasive bladder cancer (NMIBC) using diagnostic test accuracy (DTA) and network meta-analysis (NMA). EVIDENCE ACQUISITION: PubMed, Web of Science, and Scopus were searched up to April 2021 to identify studies addressing the diagnostic values of UBTs: Xpert bladder cancer, Adxbladder, Bladder EpiCheck, Uromonitor and Cxbladder Monitor, and Triage and Detect. The primary endpoint was to assess the pooled diagnostic values for disease recurrence in NMIBC patients using a DTA meta-analysis and to compare them with cytology using an NMA. The secondary endpoints were the diagnostic values for high-grade (HG) recurrence as well as for the initial detection of bladder cancer. EVIDENCE SYNTHESIS: Twenty-one studies, comprising 7330 patients, were included in the quantitative synthesis. In most of the studies, there was an unclear risk of bias. For NMIBC surveillance, novel UBTs demonstrated promising pooled diagnostic values with sensitivities up to 93%, specificities up to 84%, positive predictive values up to 67%, and negative predictive value up to 99%. Pooled estimates for the diagnosis of HG recurrence were similar to those for the diagnosis of any-grade recurrence. The analysis of the number of cystoscopies potentially avoided during the follow-up of 1000 patients showed that UBTs might be efficient in reducing the number of avoidable interventions with up to 740 cystoscopies. The NMA revealed that diagnostic values (except specificity) of the novel UBTs were significantly higher than those of cytology for the detection of NMIBC recurrence. There were too little data on UBTs in the primary diagnosis setting to allow a statistical analysis. CONCLUSIONS: Our analyses support high diagnostic accuracy of the studied novel UBTs, supporting their utility in the NMIBC surveillance setting. All of these might potentially help prevent unnecessary cystoscopies safely. There are not enough data to reliably assess their use in the primary diagnostic setting. These results have to be confirmed in a larger cohort as well as in head-to-head comparative studies. Nevertheless, our study might help policymakers and stakeholders evaluate the clinical and social impact of the implementation of these tests into daily practice. PATIENT SUMMARY: Novel urinary biomarker tests outperform cytology with the potential of improving routine clinical practice by preventing unnecessary cystoscopic examinations during the surveillance of non-muscle-invasive bladder cancer.

Additional file 4: Supplementary Table 2. Meta-regression according to methodological covariates.

Additional file 3: Supplementary Table 1. Results of asymmetry tests for publication bias assessment.

INTRODUCTION AND OBJECTIVE:Patients diagnosed with high risk features at the time of transurethral resection of the bladder (TURB) should be scheduled for a second look in consideration of the high...

BACKGROUND Intermediate-risk prostate cancer (PCa) represents a heterogeneous disease, where a non-negligible proportion of patients harbor favorable pathologic characteristics and are potentially eligible for active surveillance (AS). We aimed at developing a model for the identification of pathologically favorable PCa at radical prostatectomy (RP) among intermediate-risk patients. METHODS Overall, 3,821 intermediate-risk patients treated with RP at two centers between 2005 and 2013 were identified. Pathologically favorable PCa was defined as low-grade organ-confined disease. Age, biopsy Gleason, PSA density (PSAD), and the percentage of positive cores were included in multivariable logistic regression analyses predicting favorable PCa and formed the basis for a logistic regression-based risk calculator. The internally validated discrimination and calibration of the risk calculator were quantified using 200 bootstrap resamples. Decision curve analysis (DCA) provided an estimate of the net benefit obtained using this model versus treating no one and treating everyone. RESULTS Overall, 10.0% of all intermediate risk patients had favorable disease. In multivariable analyses, patients with biopsy Gleason score ≤6 had higher probability of favorable disease compared to those with higher-grade disease (P

To compare the clinical reliability of the 1973 and 2004 World Health Organisation (WHO) classification systems in pT1 bladder cancer.We retrospectively evaluated 291 consecutive patients who had pT1 high grade bladder cancer between 2004 and 2011. All tumours were simultaneously evaluated by a single uro-pathologist as high grade and G2 or G3. All patients underwent a second transurethral resection (TUR) and those confirmed with non-muscle-invasive bladder cancer at second TUR received bacille Calmette-Guérin. Follow-up included urine cytology and cystoscopy 3 months after second TUR and then every 6 months for 5 years. Univariate and multivariate analysis to determine recurrence-free survival (RFS) and progression-free survival (PFS) rates were performed using the Kaplan–Meier method with the log-rank test.G2 tumours were found in 124 (46.6%) and G3 in 142 (53.4%) patients. The mean (median; range) follow-up period was 31.1 (19; 1–93) months. The 5-year RFS rate was 39.1% for the overall high grade population, and 49.1 and 31.8% for G2 and G3 subgroups, respectively. The 5-year PFS was 82% for the overall high grade population and 89 and 73% for G2 and G3 subgroups, respectively. RFS (P0.002) and PFS (P0.001) rates were significantly different between the G2 and G3 subgroups. In multivariate analysis, only the grade assessed according to the 1973 WHO significantly correlated with both RFS (P = 0.003) and PFS (P0.001).The results suggest that the 1973 WHO classification system has higher prognostic reliability for patients with T1 disease. If confirmed, these findings should be carefully taken into account when making treatment decisions for patients with T1 bladder cancer.

Purpose To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)—1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR − baseline eGFR; Δ2 = 6 months eGFR − POD-1 eGFR; Δ3 = 12 months eGFR − 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. Results A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR p p = 0.003), POD-1 AKI (OR 2.88, p p p p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR p p = 0.019), hydronephrosis (p p p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p Conclusion Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC).Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site.Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p0.001) and shorter median time to recurrence (88 vs 123 months, p0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals.VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

Background: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. Methods: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. Results: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16–0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. Conclusion: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Background The prognostic role of multiparametric magnetic resonance imaging (mpMRI) and systematic biopsy in predicting biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer (PCa) patients has not been addressed yet. Objective To develop a risk tool predicting BCR after RP in patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy. Design, setting, and participants A total of 804 patients with a clinical suspicion of PCa and positive mpMRI diagnosed with MRI-targeted plus concomitant systematic biopsy treated with RP were identified. Outcome measurements and statistical analyses The outcome was represented by BCR defined as two prostate-specific antigen (PSA) values ≥0.2 ng/ml after surgery. Multivariable Cox regression analyses assessed the predictors of BCR. A risk tool model based on imaging and biopsy parameters was developed and validated internally. The c-index, calibration plot, and decision curve analyses were used to assess discrimination, calibration, and the net benefit associated with its use in predicting BCR at 36 mo. Results and limitations Median (interquartile range) follow-up was 28 (25–29) mo, and 89 patients experienced BCR. The 36-mo BCR-free survival rate was 89%. The maximum diameter of the index lesion and seminal vesicle invasion (SVI) at mpMRI as well as the presence of clinically significant PCa at systematic biopsy (defined as a grade group of >2) were associated with BCR (all p ≤ 0.03). A model based on PSA, Prostate Imaging Reporting and Data System score, SVI at mpMRI, diameter of the index lesion, grade group at MRI-targeted biopsy, and clinically significant PCa at systematic biopsy achieved the highest discrimination (77%) among all clinical models, as well as the European Association of Urology risk groups (62%) and the Cancer of the Prostate Risk Assessment (CAPRA) score (60%). This tool was characterized by excellent calibration at internal validation and the highest net benefit when predicting BCR for the threshold risk between 0% and 30%. Conclusions The adoption of predictive models accounting for mpMRI and MRI-targeted biopsy-derived variables and concomitant systematic biopsy would improve clinicians’ ability to identify patients at a higher risk of early recurrence after surgery. Patient summary The use of information obtained at multiparametric magnetic resonance imaging (mpMRI), and MRI-targeted and concomitant systematic biopsy would improve clinicians’ ability to identify prostate cancer patients at a higher risk of experiencing early biochemical recurrence after surgery.

Purpose: To assess the impact of perioperative chemotherapy on survival in cN+ BCa patients and analyze it according to the pN status. Methods: A retrospective analysis was conducted on639 BCa patients with cTanyN1-3M0 BCa treated with radical cystectomy (RC) and bilateral lymph node dissection (LND) with or without perioperative chemotherapy in ten tertiary referral centers from 1990 to 2017. Selected cN+ patients received induction chemotherapy (IC), whereas adjuvant chemotherapy (ACT) was delivered to selected pN+ patients. Univariable and multivariable Cox regression analyses were used to predict overall mortality (OM) after surgery, adjusting for clinicopathological confounders. Kaplan–Meier analyses assessed OM according to the treatment modality. Results: Overall, 356 (56%) patients were treated with surgery alone, 155 (24%) with IC followed by surgery, and 128 (20%) with ACT following surgery. Over a median follow-up of 25months, 316 deaths were recorded. At univariable analysis, patients treated with IC and surgery had lower OM both considering cN+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49–0.87, p = 0.004] and cN+pN− patients (HR 0.61, 95% CI 0.37–0.99, p = 0.05) compared to those treated with surgery alone. cN+pN+ patients treated with ACT experienced lower OM compared to those treated with IC or surgery alone at multivariable analysis (HR 0.40, 95% CI 0.22–0.74, p = 0.003). Conclusion: Patients with cTany cN+ cM0 BCa benefit more in terms of OS when treated with IC followed by RC + LND compared to RC + LND alone, regardless of LNMs at final histopathology examination. More data are needed to assess the role of ACT in the management of cN+ patients.

Context: Upper tract urothelial carcinoma (UTUC) represents the third most frequent malignancy in Lynch syndrome (LS). Objective: To systematically review the available literature focused on incidence, diagnosis, clinicopathological features, oncological outcomes, and screening protocols for UTUC among LS patients. Evidence acquisition: Medline, Scopus, Google Scholar, and Cochrane Database of Systematic Reviews were searched up to May 2021. Risk of bias was determined using the modified Cochrane tool. A narrative synthesis was undertaken. Evidence synthesis: Overall, 43 studies between 1996 and 2020 were included. LS patients exhibited a 14-fold increased risk of UTUC compared with the general population, which further increased to 75-fold among hMSH2 mutation carriers. Patients younger than 65 yr and patients with personal or family history of LS-related cancers should be referred to molecular testing on tumour specimen and subsequent genetic testing to confirm LS. Newly diagnosed LS patients may benefit from a multidisciplinary management team including gastroenterologist and gynaecologist specialists, while genetic counselling should be recommended to first-degree relatives (FDRs). Compared with sporadic UTUC individuals, LS patients were significantly younger (p = 0.005) and exhibited a prevalent ureteral location (p = 0.01). Radical nephroureterectomy was performed in 75% of patients (5-yr cancer-specific survival: 91%). No consensus on screening protocols for UTUC was achieved: starting age varied between 25-35 and 50 yr, while urinary cytology showed sensitivity of 29% and was not recommended for screening. Conclusions: Urologists should recognise patients at high risk for LS and address them to a comprehensive diagnostic pathway, including molecular and genetic testing. Newly diagnosed LS patients should be referred to a multidisciplinary team, while genetic counselling should be recommended to FDRs. Patient summary: In this systematic review, we analysed the existing literature focused on upper tract urothelial carcinoma (UTUC) among patients with Lynch syndrome (LS). Our purpose is to provide a comprehensive overview of LS-related UTUC to reduce misdiagnosis and improve patient prognosis.

Background Literature lacks clear evidence regarding the optimal treatment for non–muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies. Objective To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC. Design, setting, and participants We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19–64). Intervention Patients underwent immediate RC versus conservative management with bacillus Calmette-Guerin. Outcomes measurements and statistical analysis Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis. Results and limitations Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study. Conclusions Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis. Patient summary Bacillus Calmette-Guerin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.

Background Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies. Objective To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies. Design, setting, and participants A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified. Outcome measurements and statistical analyses Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated. Results and limitations Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC). Conclusions Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting. Patient summary We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.

Background: Improvement in postoperative risk stratification of upper tract urothelial carcinoma (UTUC) is required to better predict outcomes and counsel patients on adjuvant treatment. Objective: To validate the association between caveolin-1 and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for UTUC. Design, setting, and participants: Caveolin-1 expression was evaluated via immunochemistry on a tissue microarray from 621 patients. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positive. The median follow-up in this retrospective study was 35 mo (interquartile range 16-65). Intervention: Radical nephroureterectomy. Outcome measurements and statistical analysis: Univariate and multivariable Cox proportional hazards regression models were used to assess the association between caveolin-1 expression and recurrence and cancer-specific mortality (CSM). Results and limitations: Caveolin-1 was overexpressed in 150 patients (24%). Overexpression was associated with higher pathological stage (p< 0.001) and grade (p< 0.001). In univariate analyses, overexpression of caveolin-1 was significantly associated with lower recurrence (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.6; p = 0.004) and CSM (HR 1.8, 95% CI 1.2-2.7; p = 0.005); however, multivariable analyses did not prove its independent association with outcomes. The study is limited by its retrospective nature. Conclusions: Despite overexpression in a quarter of UTUC patients, caveolin-1 was not independently associated with oncological outcomes. Its use could be evaluated to improve clinical staging of biopsy specimens and to help in clinical decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Patient summary: Development of a panel of prognostic and predictive markers is mandatory for patient consultations in the era of personalized medicine. We evaluated the role of caveolin-1 in a large series of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) and found that it was not independently associated with oncological outcomes. Nevertheless, it was associated with adverse pathological features. Considering caveolin-1 in UTUC biopsy specimens could help in improving clinical staging and decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Caveolin-1 is associated with worse oncological features among patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), but is not independently associated with oncological outcomes. Its clinical use could be explored in UTUC biopsy specimens for improving clinical staging and helping in decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment.

Background: The use of primary androgen deprivation therapy (PADT) is common in elderly men with early-stage prostate cancer (PCa), despite the absence of guideline recommendations. Objective: To examine survival patterns of octo- and nonagenarian men with organ-confined PCa exposed to PADT, to assess whether their life expectancy warrants androgen deprivation therapy use. Design, setting, and participants: In the Surveillance, Epidemiology, and End Results-Medicare-linked database, we identified 14 785 octo- and nonagenarian organ-confined PCa patients treated with PADT between 1991 and 2009. Outcome measurements and statistical analysis: The smoothed cumulative incidence method was used to examine 10-yr overall mortality, cancer-specific mortality (CSM), and other-cause mortality (OCM) rates. Multivariable Cox regression analyses focused on the combined effect of age and Charlson comorbidity index (CCI) after adjusting for different confounders. Results and limitations: Of all the deaths observed during the study period, 80% were due to non-cancer causes and 20% were due to PCa. The 10-yr overall survival (OS) rate in the overall population was 15.4%. The 10-yr OS rates ranged from 19.9% in patients aged 80-84 yr to 3.1% in those aged ≥90 yr. Similarly, the 10-yr OS rates ranged from 18.7% in patients with CCI = 0 to 11.5% in those with CCI. ≥. 2. The 10-yr OCM rate in the overall population was 68.2%. The 10-yr OCM rates ranged from 64.6% in patients aged 80-84 yr to 77.2% in patients aged ≥90 yr. Similarly, the 10-yr OCM rates ranged from 62.1% in patients with CCI = 0 to 75.2% in those with CCI. ≥. 2. The 10-yr CSM rate in the overall population was 16.4%. The 10-yr CSM rates ranged from 15.5% in patients aged 80-84 yr to 19.7% in those aged ≥90 yr, and from 19.2% in patients with CCI = 0 to 13.3% in those with CCI. ≥. 2. Conclusions: Of the elderly patients with organ-confined PCa exposed to PADT, only 15% survive at 10-yr follow-up. Mortality related to non-cancer causes is the leading cause of death in the same follow-up period. These figures question the rationale for PADT in elderly men with organ-confined PCa. Patient summary: In this study, we looked at the survival patterns of octo- and nonagenarians treated with primary androgen deprivation therapy for organ-confined prostate cancer. We found that a small proportion of patients who received primary androgen deprivation therapy remain alive at 10-yr follow-up, and the leading cause of death was not attributable to prostate cancer. A small proportion of octo- and nonagenarians with organ-confined prostate cancer exposed to primary androgen deprivation therapy (PADT) remain alive at 10-yr follow-up. Moreover, the main cause of death in these patients is related to non-prostate cancer. Such findings question the rationale for PADT in these patients.

We assessed whether prostate cancer (PCa) location might affect oncologic outcomes after focal therapy (FT) for PCa.We identified 274 men receiving FT for PCa using either high intensity focused ultrasound (HIFU) or cryotherapy at a high volume center between 2009 and 2018. Survival analyses using Kaplan-Meier method were used to assess any additional treatment and radical treatment rates according to PCa location. Propensity-score match analysis was used to compare oncologic outcomes of HIFU vs cryotherapy according to PCa location. Covariates were prostate specific antigen, clinical stage, prostate volume, Gleason score, maximum cancer core length, percentage of positive cores and treatment modality.A total of 166 and 108 men received FT with HIFU and cryotherapy, respectively. Overall, 39% (106) and 31% (85) received at least an additional treatment and a radical treatment after FT, respectively, with a median followup of 51 months. At 36 months' followup, the rates of any additional treatment-free survival were 71%, 75%, and 69% for patients with basal, mid-prostate and apical disease, respectively (p=0.7). At multivariable logistic regression analysis, PCa location was not significantly associated with higher risk of either any additional treatment or radical treatment (all p0.4). After matching, there was no difference between HIFU vs cryotherapy in terms of any additional treatment rates according to PCa location.The PCa location does not significantly affect the rate of failure after FT. The presence of an apical lesion should not be considered an exclusion criteria for FT. Both HIFU and cryotherapy likely achieve similar medium-term oncologic results regardless of PCa location.

Context Smoking habit at the time of surgery is associated with higher perioperative complications and mortality across different types of surgeries. In recent years, several studies have attempted to explore the influence of smoking on perioperative outcomes following radical cystectomy (RC) for urothelial bladder cancer (UBC) with contradictory results. Objective To systematically investigate and meta-analyze the association between smoking habit and perioperative morbidity and mortality in UBC patients treated with RC. Evidence acquisition A systematic review of the literature published between January 2000 and January 2020 investigating the impact of smoking habit on perioperative outcomes of patients treated with RC for UBC was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Systematic Reviews of Interventions. Evidence synthesis Overall, 27 articles involving 27 854 patients were included in the systematic review, and of these, 11 studies were included in the meta-analysis. The studies included showed a moderate to high risk of bias. Smoking status (smokers vs nonsmokers) was significantly associated with the onset of major postoperative complications (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.51–2.32; I2 = 0%), infections (HR 1.34, 95% CI 1.02–1.72; I2 = 66.2%), and mortality (HR 1.84, 95% CI 1.14–2.98; I2 = 4.9%). Conclusions Smoking status at the time of RC is associated with increased risk for major postoperative complications, infections, and mortality. These results suggest the need for strict postoperative monitoring in smokers due to the increased risk of experiencing adverse events and underline the need for intensive smoking cessation interventions in the preoperative setting. Patient summary In this study, we reviewed the impact of smoking habit on perioperative outcomes following radical cystectomy (RC). Based on the available data, the impact of smoking on morbidity and mortality after RC is significant and relevant; as such, every effort should be made in the preoperative setting to encourage smoking cessation.

Background: Data regarding clinical node metastases (cN+) in patients undergoing radical cystectomy (RC) are scarce. Objective: To evaluate the performance of conventional imaging in detecting cN+ and analyze the impact of cN+ on survival among patients treated with RC without neoadjuvant chemotherapy (NAC). Design, setting, and participants: Data from three independent centers of consecutive patients with bladder cancer treated with RC without NAC were analyzed. Outcome measurements and statistical analysis: cN+ was defined as pelvic nodes >8. mm or abdominal nodes >10. mm in maximum short-axis diameter as detected via preoperative computed tomography or magnetic resonance imaging. Performance characteristics were evaluated considering pN+ disease as the reference standard. Multivariable Cox regression analyses were performed for prediction of survival. Results and limitations: Overall, 196 patients (7.1%) had cN+ disease before RC and pN+ status was confirmed for 122 of them (62.2%). cN+ status in the overall population had sensitivity of 18% and specificity of 96% with a calculated area under the curve of 57%. The median follow-up was 108 mo. On multivariable analyses, cN+pN+ (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.26-2.68) and cN-pN+ (HR 2.36, 95% CI 1.90-2.92) were predictors of CSM (both . p . 0.2). Conclusions: Our study confirms the poor accuracy of conventional preoperative imaging in assessing nodal disease status. cN status had no independent impact on survival when all confounders were evaluated, and potentially curative treatments should not be withheld on the basis of clinical nodal status alone. Patient summary: The accuracy of conventional imaging techniques for detection of pathologic lymph node-positive disease before radical cystectomy for bladder cancer is suboptimal. The presence of clinical lymph node positivity on preoperative imaging is not an independent predictor of oncologic outcomes, and if the node invasion is not confirmed at radical cystectomy, these patients may have good long-term outcomes. Conventional imaging techniques are suboptimal in detecting preoperative node metastases. The presence of node metastases on preoperative imaging is not a predictor of poor oncologic outcomes if the node invasion is not confirmed pathologically after surgery.

Background: We assessed the role of N-cadherin as a prognostic biomarker in patients with invasive bladder cancer (BCa) who had undergone radical cystectomy (RC). Patients and Methods: The present retrospective single-center study included 433 BCa patients who had undergone RC and bilateral lymph node dissection. Formalin-fixed paraffin tissue microarrays were stained with an anti-N-cadherin monoclonal mouse antibody. N-cadherin expression was considered positive if any immunoreactivity was detected. Multivariable Cox regression models were created to evaluate the prognostic effect of N-cadherin on survival. Results: N-cadherin expression was observed in 189 patients (43.7%). It was associated with advanced pathologic stage (P = .001) and lymph node metastasis (P < .001). During a median follow-up period of 10.6 years, N-cadherin expression was associated with worse recurrence-free survival, overall survival, and cancer-specific survival (P < .001, P = .001, and P < .001, respectively). On multivariable analysis adjusted for the effects of standard clinicopathologic features, N-cadherin expression retained its association with worse recurrence-free survival (hazard ratio, 1.41; 95% confidence interval, 1.02-1.92; P = .032) but not cancer-specific survival (P = .07) and overall survival (P = .3). Conclusion: N-cadherin was expressed in approximately 40% of patients with invasive BCa. Its expression was associated with features of biologically and pathologically adverse disease and worse recurrence-free survival. N-cadherin could be a part of a marker panel to help clinical decision-making and therapy for BCa.

Objective: Growing literature supports good survival expectancies in bladder cancer (BCa) patients affected by clinical node metastases (cN+) treated with multimodal therapy. We evaluated the role of adjuvant chemotherapy in cN+BCa patients treated with radical cystectomy (RC) and pelvic lymph node dissection (PLND) without neoadjuvant chemotherapy (NAC). Methods: We evaluated a total of 192 patients with BCa and cN+. All patients were treated with RC and PLND without NAC between 2001 and 2013. Kaplan–Meier analyses and Cox regression analyses were used to assess the impact of adjuvant chemotherapy (ACT) on recurrence, cancer-specific mortality (CSM) and overall mortality (OM) after surgery. Results: Overall, 99 patients (51.6%) were found without node metastases at RC, while 18 (9.4%), 58 (30.2%) and 17 (8.9%) patients were found pN1, pN2 and pN3, respectively. With a median follow-up of 48 months, in cN+ patients we recorded 5-year recurrence, CSM and OM of 55, 53 and 51%, respectively. Overall, 36 (18.8%) patients were treated with adjuvant chemotherapy. At univariable analyses, ACT was associated with improved overall survival [Hazard ratio (HR): 0.42, confidence interval (CI) 0.20–0.86, p = 0.02) in pN+ subgroup only. These results were confirmed at multivariable analyses, where ACT was associated with improved CSS (HR: 0.45, CI 0.21–0.89, p = 0.03) and OS (HR: 0.37, CI 0.17–0.81, p = 0.01). Conclusions: We report good survival outcomes in cN+ patients treated with RC. The use of ACT after surgery increases survival expectancies, especially in those patients with pathological node disease. Our data need to be further evaluated in prospective setting.

Objective: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). Patients and Methods: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2–4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with ‘doubly robust’ estimation. A 6-month landmark analysis was performed to exclude early events. Results: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally

Objective To investigate the characteristics and outcomes of late recurrence (LR) in patients with bladder cancer (BCa) treated with radical cystectomy (RC) and to identify clinicopathologic predictors of LR and postrecurrence survival. Materials and Methods This multicenter study included 1652 BCa patients. LR was defined as occurring more than 5 years after RC. Differences in postrecurrence overall survival according to the timing of disease recurrence and the location of recurrence were calculated using the log-rank test. A logistic regression model was used to identify predictors of LR, and Cox regression models were used to evaluate variables associated with postrecurrence overall survival (OS). Results Overall, 548 patients experienced disease recurrence. Of these, 67 patients (12.2%) experienced LR, with a median time to recurrence of 86 months (interquartile range 70.5-107.2). LR was more likely to be located in the urothelium (P =.005). On multivariable analysis, younger age (P =.008) and non–organ confined disease (P =.03) were found to be predictors of LR. Postrecurrence 5-year OS was worse in patients who experienced early recurrence compared with those with LR (12% vs 25%, P =.02) and in those with nonurothelial recurrence compared to those with disease recurrence in the remaining urothelium (12% vs 51%, P

Introduction We sought to describe incidence of histological variants after radical cystectomy (RC) due to bladder cancer (BCa). Moreover, we investigated survival outcomes accounting for this parameter. Methods We retrospectively evaluated data from 1,067 patients with BCa treated with RC between 1990 and 2013 at a single tertiary care referral center. All specimen were evaluated by dedicated uropathologists. Univariable and multivariable Cox regression analyses tested the effect of different histopathological variant on recurrence, cancer-specific mortality (CSM), and overall mortality (OM) after accounting for all available confounders. Results Of 1,067 patients, 729 (68.3%) harbored pure urothelial BCa while 338 (31.7%) were found to have a variant. Considering uncommon variants, 21 (2.0%) were sarcomatoid, 10 (0.9%) lymphoepitelial, 19 (1.8%) small cell, 109 (10.2%) squamous, 89 (8.3%) micropapillary, 23 (2.2%) glandular, 34 (3.2%) mixed variants, and 33 (3.1%) were found with other types of variants. With a median follow-up of 6.2 years, 343 recurrence, 365 CSM, and 451 OM were recorded, respectively. At multivariable Cox regression analyses, the presence of small cell variant was associated with higher recurrence (hazard ratio [HR] = 3.47, P 0.1). Conclusion Our study confirms that histological variant is not an infrequent event at RC specimen. However, in our single-center series, only patients found with small cell variant were associated with a negative effect on survival after RC.

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.

Purpose The effect of time between radical prostatectomy and radiation therapy on postoperative functional outcomes is still unclear in patients with surgically managed prostate cancer. We hypothesized that a shorter time between radical prostatectomy and radiotherapy might be associated with worse functional recovery rates after radical prostatectomy. Materials and Methods We retrospectively evaluated 2,190 patients treated with radical prostatectomy and stratified according to radiotherapy schedule (adjuvant radiotherapy, salvage radiotherapy, no radiotherapy). We examined recovery rates for erectile function and urinary function according to adjuvant radiotherapy, salvage radiotherapy and no radiotherapy, and according to time from surgery to radiotherapy. Cox regression analyses were used to evaluate the impact of these predictors on functional outcomes. Results Median followup was 48 months. The 3-year erectile function recovery rates were 35.0%, 29.0% and 11.6% in patients who received no radiotherapy, salvage radiotherapy and adjuvant radiotherapy, respectively (p

Objective: The study aimed to evaluate the impact of the different types of prostate involvement at the time of radical cystoprostatectomy (RCP). Methods: Data from 893 male patients treated with RCP at a referral center for bladder cancer (BCa) were assessed. Prostatic urothelial carcinoma (PUC) was stratified as stromal vs. urethral/duct involvements. Multivariable Cox regression analyses were built to test the impact of the presence of incidental prostate cancer (PCa) and PUC on survival outcomes. Results: PCa was present in 319 (35.7%) RCP patients, of which 45 (14.1%) had significant PCa disease. PUC was identified in 181 patients (20%): 75 (41.1%) with urethral/duct involvement and 106 (58.6%) with stromal. Within a median follow-up of 72 months, stromal PUC, but not the other forms of PUC or PCa, was associated with worse survival outcomes. In multivariable analyses adjusted for the effects of standard features, stromal PUC remained associated with recurrence (hazards ratio [HR] 2.01, p = 0.03), cancer-specific mortality (HR 1.65, p = 0.01), and overall mortality (HR 1.45, p = 0.03). Conclusion: Prostatic stromal invasion with urothelial carcinoma confers a poor survival expectation to BCa patients after surgical treatment. Conversely, other type of urothelial prostatic invasions or the presence of concomitant PCa does not seem to be associated with differences in survival outcomes.

Bladder cancer (BCa) is the second most common genitourinary malignancy with 81,190 estimated new diagnosis in the 2018 in the United States only (1). Radical cystectomy (RC) with bilateral pelvic node dissection (PLND) represents the gold standard for very recurrent high risk non-muscle invasive tumors and for muscle invasive BCa (2).

Radical cystectomy (RC) is associated with significant complication rates, however, no data exist about incidence of readmission after RC in European series that are characterized by longer length of stay (LOS) compared with American series. We found a rate of 12% of 30-day readmission, moreover, an increase of LOS seems effective to prevent readmission only in patients older than 70 years. Introduction Previous studies showed high hospital readmission rates after radical cystectomy (RC) for bladder cancer (BCa), however at the time results of a European series analyzing this event were still missing. Patients and Methods Overall, 1090 consecutive BCa patients treated with RC at a single center between January 2002 and August 2012 were identified. Logistic regression analyses were used to test the association between covariates and 30-day readmission in the overall population and after stratifying according age at the time of surgery. Results Mean length of stay (LOS) was 19 days (median, 16 days), and the overall 30-day readmission rate was 12.2%. The most frequent reasons for readmission at 30 days were ileus (n = 15; 11.3%), lymphoceles (n = 11; 8.3%), wound infection (n = 10; 7.5%), and fever (n = 12; 9.0%). In multivariable logistic regression analysis, age (odds ratio [OR], 1.02; P = .04) and LOS (OR, 0.94; P < .01) were associated with 30-day readmission. However, when analyzed according age at the time of surgery, a beneficial effect from a longer LOS was observed only in patients older than 70 years (P < .003). Conclusion In the first European series on the effect of 30-day readmission, our data showed that even with a relative high mean LOS, 30-day readmission remained an ineradicable factor. Of note, older patients and shorter LOS were associated with an increased risk of readmission at 30 days, however, an increase of LOS to prevent readmission seemed effective only in patients older than 70 years.

Introduction Several definitions of erectile function (EF) recovery after bilateral nerve-sparing radical prostatectomy (BNSRP) have been proposed based on the results of the International Index of EF (IIEF). Aim We aimed at evaluating overall satisfaction (OS) after BNSRP according to the ability to achieve the pretreatment EF. Methods We evaluated data of 652 patients treated with BNSRP for clinically localized prostate cancer (PCa). Erectile dysfunction (ED) was classified according to the IIEF-EF domain score. Return to baseline EF was defined as patients who reached the same preoperative ED category during the 3-year follow-up. Cox regression analyses were fitted to predict return to baseline IIEF-EF and to predict OS defined according to the IIEF-OS in the overall population. Logistic regression analyses were performed to analyze OS in men who reached the back to baseline status. Main Outcome Measures The outcome of the study was to evaluate back to baseline EF status and to correlate it with postoperative OS. Results Preoperative satisfaction was reported by 218 (33.4%) patients. Postoperative satisfaction was achieved by 103 patients. Overall, 383 patients were able to achieve the preoperative IIEF-EF score. However, only 26.9% reported being satisfied. Age and preoperative IIEF-EF score were significantly associated with baseline IIEF-EF recovery (all P ≤ .02). Patients who were able to return to baseline IIEF-EF were more likely to be satisfied (P < .001). Time elapsed between surgery and achievement of baseline IIEF-EF was significantly associated with OS (P < .001). Among patients who were able to achieve the baseline IIEF-EF score, a preoperative IIEF-EF of 22–25 and 26–30 was significantly associated with postoperative satisfaction (all P < .001). Conclusion After BNSRP, reaching the baseline IIEF-EF score is not always sufficient to obtain patient satisfaction. Only patients with a preoperative IIEF-EF ≥22 who reached the baseline score after surgery considered themselves satisfied. This should be taken into account in preoperative patient counseling.

Objective: The impact of positive surgical margin (SM) on cancer control outcomes in prostate cancer patients is a subject of continuous debate. We test the hypothesis that the impact of SM on clinical recurrence (CR) rate may vary based on the other clinical/pathologic characteristics of the tumor. Materials and Methods: We focused on 5290 patients treated with robot-assisted radical prostatectomy and pelvic node dissection, between 2002 and 2013, at three tertiary care centers. Regression tree analysis stratified patients into risk groups based on their tumor characteristics and the corresponding CR rate. Kaplan-Meier log-rank and multivariable Cox regression models tested the relationship between SM status and CR rate in each tree-generated risk group. Results: Mean (median) follow-up time was 47.7 (39.0) months. Regression tree analysis that considered all available covariates, except SM status, divided patients based on their CR risk into the following risk groups: (1) high risk (any pT3b/pT4 disease); (2) intermediate risk (≤pT3a disease and pGS 8-10); (3) low risk (≤pT3a, pGS ≤7, and prostate-specific antigen [PSA] >9 ng/mL); and (4) very low risk (≤pT3a, pGS ≤7, and PSA ≤9 ng/mL). Positive SM had a significant detrimental impact on CR risk only in two groups: intermediate risk (p < 0.001) and high risk (p = 0.01). These observations were confirmed by multivariable analyses. Conclusions: Our findings show that positive SM had a detrimental impact on CR only in a minority of patients (15%), specifically in those with advanced pathologic stage and/or pathologically poorly differentiated tumor. For all the remaining patients (85%), positive SM by itself did not increase the risk of CR.

Introduction To develop and externally validate a novel nomogram aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT). Materials & methods The development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 with subsequent BCR, defined as two subsequent prostate-specific antigen values >0.2 ng/ml. Multivariable competing-risks regression analyses tested the predictors of CSM after BCR for the purpose of 5-year CSM nomogram development. Validation (2000 bootstrap resamples) was internally tested. External validation was performed into a population of 6734 PCa patients with BCR after treatment with RP at the Mayo Clinic from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method. Results The 5-year CSM-free survival rate was 83.6% (confidence interval [CI]: 79.6–87.2). In multivariable analyses, pathologic stage T3b or more (hazard ratio [HR]: 7.42; p = 0.008), pathologic Gleason score 8–10 (HR: 2.19; p = 0.003), lymph node invasion (HR: 3.57; p = 0.001), time to BCR (HR: 0.99; p = 0.03) and age at BCR (HR: 1.04; p = 0.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0–91.7%). External validation of our nomogram showed a good PA at 83.2%. Conclusions We developed and externally validated the first nomogram predicting 5-year CSM applicable to contemporary patients with BCR after RP with or without adjuvant treatment.

Background: The Deyo/Charlson co-morbidity index (CCI) and Klabunde co-morbidity index (KCI) co-morbidity indexes represent outdated indexes when the endpoint of complications after radical prostatectomy (RP) is considered. A novel group of co-morbidities derived from International Classification of Diseases-9 diagnostic codes in a contemporary RP database could provide better accuracy. Research Design, Subjects and Measures: We relied on 20,484 patients with clinically localized non-metastatic prostate cancer treated with RP between 2000 and 2009 in the Surveillance, Epidemiology, and End Results-Medicare linked database. We examined 2 endpoints, namely, 90-day medical complication rate and 90-day surgical complication rate after RP. Simulated annealing (SA) was used to develop a novel co-morbidity index. Finally, the newly identified groups of co-morbid conditions were compared with the CCI and Klabunde indexes. Results: Our SA identified 10 and 7 individual co-morbid conditions able to predict 90-day medical and surgical complications respectively. This novel model showed improved predictive accuracy over CCI and KCI for the 2 endpoints considered (respectively: 59.4 vs. 58.1 and 58.0% for medical complications, 58.0 vs. 56.8 and 56.7% for surgical complications). Conclusions: The newly defined groupings of co-morbid conditions resulted in better ability to predict the 2 endpoints of interest compared to CCI and KCI. However, the gain was marginal. This implies that better tools should be defined to more accurately predict these outcomes.

We analyzed prognostic factors and developed a prediction tool for exclusive locoregional (pelvic) recurrences after radical cystectomy for bladder cancer. We identified a subgroup of patients with the highest risk who might be best suited for clinical studies. BACKGROUND: Limited information is available about the pattern of relapse after perioperative chemotherapy with radical cystectomy (RC) vs. RC alone in muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 1082 patients of the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium database, treated from February 1990 to December 2013 at 27 centers in the United States, Europe, Israel, and Canada, were collected. Locoregional relapse was defined as any pelvic lymph node or soft tissue-only recurrences. Cumulative incidence methods were used to estimate time to locoregional relapse (TTR(L)). Cox regression analyses were performed and a nomogram for 12-month locoregional relapse-free survival (RFS) was developed. The nomogram was applied to an external data set (n = 1021). RESULTS: A total of 517 patients (47.8%) developed a relapse: 177 (16.4%) exclusive locoregional relapse. In multivariable analyses, perioperative chemotherapy was associated with longer TTR(L) (P < .001). Other factors were nonurothelial histology (P = .013), pT-stage (P < .001), and surgical margins (P < .001). The concordance index of the model was 0.681 (95% bootstrapped confidence interval, 0.666–0.716). Risk group categories were obtained according to nomogram tertiles. Despite, overall, observed locoregional RFS in the validation cohort exceeding predicted results, for high-risk patients (80 points or less, lowest nomogram tertile) observed 12-month RFS was similar between development and validation cohorts (60.1% and 66.6%). The study is limited by its retrospective nature. CONCLUSION: In the largest study, to our knowledge, that analyzed locoregional recurrences after RC, we propose a risk prediction tool for exclusive locoregional failures that might be suitable for clinical studies. Patients best suited for adjuvant radiotherapy might be those within the lowest nomogram tertile. Prospective trials are needed to validate findings.

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.

A role for local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies has been proposed. However, no data are available to identify men who would benefit from RP in this setting.To identify predictors of clinical recurrence (CR) in surgically managed PCa patients with clinical lymphadenopathies.We identified 162 patients with lymphadenopathies treated with RP and lymph node dissection at three referral centers.CR was defined as the onset of metastases detected by conventional imaging. Kaplan-Maier analyses assessed time to CR after stratifying patients according to the site of lymphadenopathies and nodal burden. Regression tree analysis stratified patients into risk groups on the basis of their preoperative characteristics.Overall, 80% of patients had lymphadenopathies in the pelvis alone and 20% in the retroperitoneum±pelvis. The median size of positive nodes was 13mm. A total of 84 patients (52%) received neoadjuvant androgen deprivation therapy and 127 (78%) had pathological lymph node invasion. The median follow-up for survivors was 64 mo. The 8-yr CR-free and CSM-free survival rates were 59% and 80%, respectively. Biopsy grade group and preoperative nodal burden should identify patients more likely to experience CR. While10% of men with biopsy grade group 1-3 and two or fewer clinical lymphadenopathies developed CR, up to 60% of patients with biopsy grade group 4-5 and retroperitoneal node involvement ultimately experienced CR at 8 yr after RP. The discrimination of the regression tree was 76% according to the area under the receiver operating characteristic curve. Our study is limited by potential unmeasured confounders and the relatively small sample size.Surgery in a multimodal setting might play a role in PCa patients with biopsy grade group 1-3 and/or enlarged nodes in the pelvis. Conversely, grade group 4-5 PCa and lymphadenopathies in the retroperitoneum are associated with worse oncologic outcomes.Approximately half of prostate cancer patients with clinical lymphadenopathies treated with radical prostatectomy are free from metastases at 8-yr follow-up. Radical prostatectomy with or without systemic therapies might play a role in selected patients with biopsy grade group 1-3 disease and/or enlarged nodes in the pelvis. Conversely, a higher grade group and the presence of lymphadenopathies in the retroperitoneum should identify candidates for systemic therapies upfront.

Introduction: Bladder cancer (BCa) is three-to-four times more common in men than in women. To explain this gender gap, several theories have been proposed, including the impact of androgen hormones. The aim of this study was to investigate the differential impact of androgen deprivation therapy (ADT) on subsequent risk of developing BCa in men with prostate cancer (PCa). Methods: A total of 196,914 patients diagnosed with histologically confirmed localized PCa between 2000 and 2009 were identified in the SEER-Medicare insurance program-linked database. Competing-risk regression analyses were performed to assess the risk of developing BCa adjusting for the risk of all-cause mortality. Univariable and multivariable competing-risk regression analyses were performed to test the effect of ADT on BCa incidence for each PCa treatment modality. Results: Of the 196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median (IQR) follow-up was 59 (29–95) months. Overall, a total of 2495 (1.3%) individuals developed BCa during follow-up. After stratification according to ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65–1.85). In the untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83–2.15). In multivariable competing-risk regression, the use of ADT was not associated with BCa, after accounting for the risk of dying from any cause (p = 0.1). Conclusion: We failed to identify any impact of ADT on the risk of developing a subsequent BCa even after stratifying according to the type of treatment. Further studies are required to explain the gender gap in BCa incidence and outcomes.

To examine the rates of adherence to guidelines for pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and to identify predictors of omitting PLND. We relied on 66,208 patients treated with RC between 2004 and 2013 within the National Inpatients Sample (NIS) database. We examined the rates of PLND according to year of surgery, patient and hospital characteristics. Univariate and multivariate logistic regression analyses assessed the probability of PLND use, after adjusting for year of surgery, age, gender, race, comorbidities, hospital location, teaching status and hospital surgical volume. Overall, PLND was performed on 54,223 (81.9%) RC patients. The rates PLND at RC significantly increased over the study period from 72.3% in 2004 to 85.9% in 2013, (p