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Moschini M.,URI Integrated Regional University Brazil | Carroll P.R.,University of California at San Francisco | Eggener S.E.,University of Chicago | Epstein J.I.,Johns Hopkins Medical Institutions | And 3 more authors.
European Urology | Year: 2017

Context: The incidence of low-risk prostate cancer (PCa) has increased as a consequence of prostate-specific antigen testing. Objective: In this collaborative review article, we examine recent literature regarding low-risk PCa and the available prognostic and therapeutic options. Evidence acquisition: We performed a literature review of the Medline, Embase, and Web of Science databases. The search strategy included the terms: prostate cancer, low risk, active surveillance, focal therapy, radical prostatectomy, watchful waiting, biomarker, magnetic resonance imaging, alone or in combination. Evidence synthesis: Prospective randomized trials have failed to show an impact of radical treatments on cancer-specific survival in low-risk PCa patients. Several series have reported the risk of adverse pathologic outcomes at radical prostatectomy. However, it is not clear if these patients are at higher risk of death from PCa. Long-term follow-up indicates the feasibility of active surveillance in low-risk PCa patients, although approximately 30% of men starting active surveillance undergo treatment within 5 yr. Considering focal therapies, robust data investigating its impact on long-term survival outcomes are still required and therefore should be considered experimental. Magnetic resonance imaging and tissue biomarkers may help to predict clinically significant PCa in men initially diagnosed with low-risk disease. Conclusions: The incidence of low-risk PCa has increased in recent years. Only a small proportion of men with low-risk PCa progress to clinical symptoms, metastases, or death and prospective trials have not shown a benefit for immediate radical treatments. Tissue biomarkers, magnetic resonance imaging, and ongoing surveillance may help to identify those men with low-risk PCa who harbor more clinically significant disease. Patient summary: Low-risk prostate cancer is very common. Active surveillance has excellent long-term results, while randomized trials have failed to show a beneficial impact of immediate radical treatments on survival. Biomarkers and magnetic resonance imaging may help to identify which men may benefit from early treatment. The incidence of low-risk prostate cancer has increased in recent years; however, only a few patients die from the disease while no survival benefit has been shown with local treatment. Biomarkers and imaging may help to identify patients with clinically significant disease. © 2017 European Association of Urology.

Briganti A.,San Raffaele Scientific Institute | Spahn M.,University of Würzburg | Joniau S.,University Hospitals Leuven | Gontero P.,University of Turin | And 14 more authors.
European Urology | Year: 2013

Background: Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease. Objective: To examine the risk of 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathologic characteristics of patients treated with radical prostatectomy (RP) for high-risk PCa. Design, setting, and participants: Within a multi-institutional cohort, 3828 men treated with RP for high-risk PCa (defined as the presence of at least one of these risk factors: prostate-specific antigen >20 ng/ml, biopsy Gleason score 8-10, clinical stage ≥T3) were identified. Intervention: All patients underwent RP and pelvic lymph node dissection. Outcome measurements and statistical analysis: Competing-risk Poisson regression analyses were performed to simultaneously assess the 10-yr CSM and OCM rates after RP. The same analyses were also conducted after stratification of patients according to age at surgery, comorbidity status assessed by the Charlson Comorbidity Index (CCI), and number of risk factors (one vs two or more). Results and limitations: Overall, 229 patients (5.9%) died from PCa; 549 (14.3%) died from other causes. The 10-yr CSM and OCM rates ranged from 5.1% to 12.8% and from 4.3% to 37.4%, respectively. Age and CCI were the major determinants of OCM; their impact on CSM was minimal. OCM was the leading cause of death in all patient groups except in young men (≤59 yr) with no comorbidities, regardless of the number of risk factors (10-yr CSM and OCM 6.9-12.8% and 5.5-6.3%, respectively). The main limitation was the lack of patients managed conservatively. Conclusions: Even in the context of high-risk PCa, long-term CSM after RP is modest and represents the leading cause of death only in young, healthy patients. Conversely, older and sicker patients with multiple risk factors are at the highest risk of dying from OCM while sharing very low CSM rates. © 2012 European Association of Urology.

Trinh Q.-D.,University of Montréal | Trinh Q.-D.,Ford Motor Company | Bianchi M.,University of Montréal | Bianchi M.,Vita-Salute San Raffaele University | And 9 more authors.
European Urology | Year: 2013

Background: The risk of in-hospital mortality after cytoreductive nephrectomy (CNT) is non-negligible and may vary widely according to various patient and hospital characteristics and clinical contexts. Objective: To better elucidate the mechanisms underlying variability in operative mortality after CNT. Design, setting, and patients: Using the US-based Nationwide Inpatient Sample registry, a weighted estimate of 16 285 patients with metastatic renal cell carcinoma (mRCC) treated with CNT between 1998 and 2007 was made retrospectively. Outcome measurements and statistical analysis: Failure to rescue (FTR), defined as the number of deaths in patients who developed an adverse outcome during hospitalization. Univariable and multivariable logistic regression models were used. Results: Of all 16 285 mRCC patients who underwent a CNT, 31% had an occurrence of one complication or more. The overall FTR rate was 5% and differed significantly according to age (≥75 yr vs <75 yr: 7.9% vs 4.3%) and comorbidities (≥3 vs 0: 7.7% vs 4.8%), as well as hospital bed size (small vs large: 7.2% vs 5.3%, all p ≤ 0.03). Patients who had an occurrence of infections (19.3%), cardiac- (15.7%), respiratory- (11.4%), or vascular-related complications (16.5%) had significantly higher FTR rates. It is noteworthy that increasing hospital volume and number of hospital beds also corresponded to lower rates of FTR after adjusting for other covariates. Conclusions: Following CNT for mRCC, the occurrence of infections, cardiac-, respiratory-, or vascular-related complications resulted in higher FTR rates. Hospitals with greater number of beds and higher annual hospital volume had lower FTR rates, confirming the concepts that support FTR as an indicator for better quality of care following a high-risk surgical procedure. Crown Copyright © 2012 Published by Elsevier B.V. on behalf of European Association of Urology. All rights reserved.

Kuru T.H.,RWTH Aachen | Futterer J.J.,Radboud University Nijmegen | Schiffmann J.,Prostate Cancer Center Hamburg Eppendorf | Porres D.,RWTH Aachen | And 2 more authors.
European Urology Focus | Year: 2015

Context: Debates on overdiagnosis and overtreatment of prostate cancer (PCa) are ongoing and there is still huge uncertainty regarding misclassification of prostate biopsy results. Several imaging techniques that have emerged in recent years could overcome over- and underdiagnosis in PCa. Objective: To review the literature on transrectal ultrasound (TRUS)-based techniques (contrast enhancement, HistoScanning, elastography) and magnetic resonance imaging (MRI)-based techniques for a nonsystematic overview of their benefits and limitations. Evidence acquisition: A comprehensive search of the PubMed database between August 2004 and August 2014 was performed. Studies assessing grayscale TRUS, contrast-enhanced (CE)-TRUS, elastography, HistoScanning, multiparametric MRI (mpMRI), and MRI-TRUS fusion biopsy were included. Publications before 2004 were included if they reported the principle or the first clinical results for these techniques. Evidence synthesis: Grayscale TRUS alone cannot detect PCa foci (detection rate 23-29%). TRUS-based (elastography) and MRI-based techniques (MRI-TRUS fusion biopsy) have significantly improved PCa diagnostics, with sensitivity of 53-74% and specificity of 72-95%. HistoScanning does not provide convincing or homogeneous results (specificity 19-82%). CE-TRUS seems to be user dependent; it is used in a low number of high-volume centers and has wide ranges for sensitivity (54-79%) and specificity (42-95%). For all the techniques reviewed, prospective multicenter studies with consistent definitions are lacking. Conclusions: Standard grayscale TRUS is unreliable for PCa detection. Among the techniques reviewed, mpMRI and MRI-TRUS fusion biopsy seem to be suitable for enhancing PCa diagnostics. Elastography shows promising results according to the literature. CE-TRUS yields very inhomogeneous results and might not be the ideal technique for clinical practice. The value of HistoScanning must be questioned according to the literature. Patient summary: New imaging modalities such as elastography and magnetic resonance imaging/transrectal ultrasound fusion biopsies have improved the detection of prostate cancer. This may lower the burden of overtreatment as a result of more precise diagnosis. Diagnosis of prostate cancer using gray-scale transrectal ultrasound (TRUS) alone seems to be unreliable. Elastography, multiparametric magnetic resonance imaging (MRI), and MRI/TRUS fusion biopsy seem to bring clinical benefit to the diagnosis of prostate cancer. © 2015 European Association of Urology.

Gandaglia G.,University of Montréal | Gandaglia G.,Vita-Salute San Raffaele University | Popa I.,University of Montréal | Abdollah F.,Vita-Salute San Raffaele University | And 8 more authors.
European Urology | Year: 2014

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

Trinh Q.-D.,Ford Motor Company | Trinh Q.-D.,University of Montréal | Sammon J.,Ford Motor Company | Sun M.,University of Montréal | And 13 more authors.
European Urology | Year: 2012

Background: Prior to the introduction and dissemination of robot-assisted radical prostatectomy (RARP), population-based studies comparing open radical prostatectomy (ORP) and minimally invasive radical prostatectomy (MIRP) found no clinically significant difference in perioperative complication rates. Objective: Assess the rate of RARP utilization and reexamine the difference in perioperative complication rates between RARP and ORP in light of RARP's supplanting laparoscopic radical prostatectomy (LRP) as the most common MIRP technique. Design, setting, and participants: As of October 2008, a robot-assisted modifier was introduced to denote robot-assisted procedures. Relying on the Nationwide Inpatient Sample between October 2008 and December 2009, patients treated with radical prostatectomy (RP) were identified. The robot-assisted modifier (17.4x) was used to identify RARP (n = 11 889). Patients with the minimally invasive modifier code (54.21) without the robot-assisted modifier were classified as having undergone LRP and were removed from further analyses. The remainder were classified as ORP patients (n = 7389). Intervention: All patients underwent RARP or ORP. Measurements: We compared the rates of blood transfusions, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Multivariable logistic regression analyses of propensity score-matched populations, fitted with general estimation equations for clustering among hospitals, further adjusted for confounding factors. Results and limitations: Of 19 462 RPs, 61.1% were RARPs, 38.0% were ORPs, and 0.9% were LRPs. In multivariable analyses of propensity score-matched populations, patients undergoing RARP were less likely to receive a blood transfusion (odds ratio [OR]: 0.34; 95% confidence interval [CI], 0.28-0.40), to experience an intraoperative complication (OR: 0.47; 95% CI, 0.31-0.71) or a postoperative complication (OR: 0.86; 95% CI, 0.77-0.96), and to experience a pLOS (OR: 0.28; 95% CI, 0.26-0.30). Limitations of this study include lack of adjustment for tumor characteristics, surgeon volume, learning curve effect, and longitudinal follow-up. Conclusions: RARP has supplanted ORP as the most common surgical approach for RP. Moreover, we demonstrate superior adjusted perioperative outcomes after RARP in virtually all examined outcomes. © 2011 European Association of Urology.

Gandaglia G.,University of Montréal | Karakiewicz P.I.,University of Montréal | Briganti A.,Unit of Urology | Passoni N.M.,Unit of Urology | And 5 more authors.
European Urology | Year: 2015

Background Limited data exist on the impact of the site of metastases on survival in patients with stage IV prostate cancer (PCa). Objective To investigate the role of metastatic phenotype at presentation on mortality in stage IV PCa. Design, setting, and participants Overall, 3857 patients presenting with metastatic PCa between 1991 and 2009, included in the Surveillance Epidemiology and End Results-Medicare database were evaluated. Outcome measurements and statistic analyses Overall and cancer-specific survival rates were estimated in the overall population and after stratifying patients according to the metastatic site (lymph node [LN] alone, bone, visceral, or bone plus visceral). Multivariable Cox regression analyses tested the relationship between the site of metastases and survival. All analyses were repeated in a subcohort of patients with a single metastatic site involved. Results and limitations Respectively, 2.8%, 80.2%, 6.1%, and 10.9% of patients presented with LN, bone, visceral, and bone plus visceral metastases at diagnosis. Respective median overall survival and cancer-specific survival were 43 mo and 61 mo for LN metastases, 24 mo and 32 mo for bone metastases, 16 mo and 26 mo for visceral metastases, and 14 mo and 19 mo for bone plus visceral metastases (p < 0.001). In multivariable analyses, patients with visceral metastases had a significantly higher risk of overall and cancer-specific mortality versus those with exclusively LN metastases (p < 0.001). The unfavorable impact of visceral metastases persisted in the oligometastatic subgroup. Our study is limited by its retrospective design. Conclusions Visceral involvement represents a negative prognostic factor and should be considered as a proxy of more aggressive disease in patients presenting with metastatic PCa. This parameter might indicate the need for additional systemic therapies in these individuals. Patient summary Patients with visceral metastases should be considered as affected by more aggressive disease and might benefit from the inclusion in clinical trials evaluating novel molecules. © 2014 European Association of Urology.

Sun M.,University of Montréal | Bianchi M.,University of Montréal | Bianchi M.,Vita-Salute San Raffaele University | Hansen J.,Prostate Cancer Center Hamburg Eppendorf | And 11 more authors.
European Urology | Year: 2012

Context: Chronic kidney disease (CKD) is a worldwide health threat associated with increased cardiovascular disease and mortality. Objective: To examine postoperative CKD in patients with small renal masses (SRMs) treated with partial nephrectomy (PN) or radical nephrectomy (RN). Design, setting, and participants: A US National Cancer Institute Surveillance Epidemiology and End Results (SEER)-Medicare-linked retrospective cohort of 4633 T1aN0M0 renal cell carcinoma (RCC) patients who underwent PN or RN. Outcome measurements and statistical analysis: The primary outcome of interest was the onset of CKD stage ≥3. Secondary end points comprised acute renal failure (ARF), chronic renal insufficiency (CRI), anemia in CKD, and end-stage renal disease (ESRD). Kaplan-Meier and Cox regression analyses were performed. Results and limitations: Postpropensity matching resulted in 840 RN and PN patients. In multivariable analyses, RN patients were 1.9-, 1.4-, 1.8-, and 1.8-fold more likely to have an occurrence of CKD, ARF, CRI, and anemia in CKD, respectively (all p ≤ 0.004). The risk of ESRD between treatment groups failed to achieve statistical significance (p = 0.06). Conclusions: PN is associated with more favorable postoperative renal function outcomes relative to RN in the setting of SRMs. © 2012 European Association of Urology.

Sun M.,University of Montréal | Trinh Q.-D.,University of Montréal | Trinh Q.-D.,Ford Motor Company | Bianchi M.,University of Montréal | And 10 more authors.
European Urology | Year: 2012

Background: Partial nephrectomy (PN) may better protect against other-cause mortality (OCM) when compared with radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC). Objective: Test the effect of treatment type on OCM. Design, setting, and participants: Using the Surveillance Epidemiology and End Results-Medicare-linked database, 4956 RN patients (82%) and 1068 PN patients (18%) with T1a RCC were identified (1988-2005). Measurements: To adjust for inherent differences between treatment types, we relied on propensity-matched analyses. One-to-one matching was performed according to age, sex, race, baseline Charlson comorbidity index (CCI), baseline diagnosis of hypercalcemia and hyperlipidemia, socioeconomic status (SES), population density, tumor size, and year of surgery. The 2- and 5-yr OCM rates were computed using cumulative incidence. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Adjustment was made for cancer-specific mortality (CSM), patient age, CCI, sex, race, SES, tumor grade, and year of surgery. Results and limitations: Following propensity-based matching, 1068 RN patients were matched with 1068 PN patients. The 2- and 5-yr OCM rates after nephrectomy were 5.0% and 16.0% for PN versus 6.9% and 18.1% for RN, respectively. In the postpropensity multivariable analyses, patients who underwent PN were significantly less likely to die of OCM compared with their RN-treated counterparts (hazard ratio [HR]: 0.83; 95% confidence interval, 0.69-0.98; p = 0.04). Increasing age (HR: 1.08, p < 0.001), higher CCI (HR: 1.14, p < 0.001), female gender (HR: 0.79, p = 0.02), baseline hypercalcemia (HR: 2.05, p = 0.03), baseline hyperlipidemia (HR: 0.73, p = 0.003), and year of surgery (HR: 0.95, p = 0.003) were independent predictors of OCM. Conclusions: Compared with PN-treated patients, RN-treated patients are more likely to die of OCM after surgery, even after adjusting for CSM, as well as baseline CCI. Consequently, PN should be offered whenever technically feasible. Crown Copyright © 2011 Published by Elsevier B.V. on behalf of European Association of Urology. All rights reserved.

Sun M.,University of Montréal | Becker A.,University of Montréal | Becker A.,Prostate Cancer Center Hamburg Eppendorf | Tian Z.,University of Montréal | And 7 more authors.
European Urology | Year: 2014

Background For elderly individuals with localized renal cell carcinoma (RCC), surgical intervention remains the primary treatment option but may not benefit patients with limited life expectancy. Objective To calculate the trade-offs between surgical excision and nonsurgical management (NSM) with respect to competing causes of mortality. Design, setting, and participants Relying on a cohort of Medicare beneficiaries, all patients with nonmetastatic node-negative T1 RCC between 1988 and 2005 were abstracted. Intervention All patients were treated with partial nephrectomy (PN), radical nephrectomy (RN), or NSM. Outcome measurements and statistical analysis Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were modeled through competing-risks regression methodologies. Instrumental variable analysis was used to account for the potential biases associated with measured and unmeasured confounders. Results and limitations A total of 10 595 patients were identified. In instrumental variable analysis, patients treated with PN (hazard ratio [HR]: 0.45; 95% confidence interval [CI], 0.24-0.83; p = 0.01) or RN (HR: 0.58; 95% CI, 0.35-0.96; p = 0.03) had a significantly lower risk of CSM than those treated with NSM. In subanalyses restricted to patients ≥75 yr, the instrumental variable analysis failed to detect any statistically significant difference between PN (HR: 0.48; p = 0.1) or RN (HR: 0.57; p = 0.1) relative to NSM with respect to CSM. Similar trends were observed in T1a RCC only. Conclusions PN or RN is associated with a reduction of CSM among older patients diagnosed with localized RCC, compared with NSM. The same benefit failed to reach statistical significance among patients ≥75 yr. The harms of surgery need to be weighed against the marginal survival benefit for some patients. © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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