Publications by authors named "Franziska Stolzenbach"

22 Publications

  • Page 1 of 1

Tumor Size Predicts Muscle-invasive and Non-organ-confined Disease in Upper Tract Urothelial Carcinoma at Radical Nephroureterectomy.

Eur Urol Focus 2021 Mar 15. Epub 2021 Mar 15.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Canada.

Background: Pathological stage and grade of renal pelvis urothelial carcinoma (RPUC) are difficult to estimate before radical nephroureterectomy (RNU).

Objective: To examine tumor size as an independent predictor of muscle-invasive and/or non-organ-confined rates of RPUC at RNU.

Design, Setting, And Participants: Within the Surveillance, Epidemiology and End Results (SEER) database (2004-2016), we identified nonmetastatic RPUC at RNU.

Outcome Measurements And Statistical Analysis: First, we examined stage and grade distributions. Second, two separate univariable and subsequent multivariable logistic regression models (LRMs) were fitted to test the association between tumor size and the rate of (1) muscle-invasive or higher (pT2-4N0-2) and (2) non-organ-confined (pT3-4N0-2) RPUC at RNU.

Results And Limitations: Of 4657 patients, 3052 (65.5%) had pT2-4N0-2 and 2382 (51.2%) pT3-4N0-2 RPUC at RNU. The median tumor size was 3.7 cm (interquartile range 2.5-5.0). The high-grade RPUC rate ranged from 71.1% to 87.2% (p < 0.001) among SEER registries. Conversely, no differences were recorded for stage (p > 0.05) or tumor size (p = 0.1) across all registries. Rates of pT2-4N0-2 and pT3-4N0-2 RPUC increased with tumor size. Specifically, for tumor size intervals from 0.1-1.0 cm to 9.1-10.0 cm, the pT2-4N0-2 rate ranged from 45% to 83% and the pT3-4N0-2 rate ranged from 23% to 75%, respectively (both p < 0.001). In multivariable LRMs, tumor size (in 1-cm units) was an independent predictor of pT2-4N0-2 (odds ratio [OR] 1.25; p < 0.001) and pT3-4N0-2 (OR 1.30; p < 0.001) disease at RNU.

Conclusions: Tumor size is a key predictor of muscle-invasive or non-organ-confined RPUC. Greater tumor size directly and virtually linearly predicts a higher rate of invasive or non-organ-confined RPUC at RNU.

Patient Summary: For patients with cancer in urinary tract cells lining the kidney, larger tumor size predicts worse stage of the disease at surgery.
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http://dx.doi.org/10.1016/j.euf.2021.03.003DOI Listing
March 2021

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

Jpn J Clin Oncol 2021 Feb 27. Epub 2021 Feb 27.

Department of Urology, Medical University of Vienna, Vienna, Austria.

Objective: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort.

Materials And Methods: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints.

Results: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024).

Conclusions: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.
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http://dx.doi.org/10.1093/jjco/hyab023DOI Listing
February 2021

Comparison between small renal masses 0-2 cm vs. 2.1-4 cm in size: A population-based study.

Urol Oncol 2021 Apr 16;39(4):239.e1-239.e7. Epub 2021 Feb 16.

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada; Division of Urology, University of Montreal Hospital Center (CHUM), Montreal, Quebec, Canada.

Background: The NCCN guidelines recommend active surveillance (AS) as an option for the initial management of cT1a 0-2 cm renal lesions. However, data about comparison between renal cell carcinoma (RCC) 0-2 cm vs. 2.1-4 cm are scarce.

Methods: Within the Surveillance, Epidemiology, and End Results database (2002-2016), 46,630 T1a NM stage patients treated with nephrectomy were identified. Data were tabulated according to histological subtype, tumor grade (low [LG] vs. high [HG]), as well as age category and gender. Additionally, rates of synchronous metastases were quantified.

Results: Overall, 69.3 vs. 74.1% clear cell, 21.4 vs. 17.6% papillary, 6.9 vs. 6.8% chromophobe, 2.0 vs. 1.1% sarcomatoid dedifferentiation, 0.2 vs. 0.2% collecting duct histological subtype were identified for respectively 0-2 cm and 2.1-4 cm RCCs. In both groups, advanced age was associated with higher rate of HG clear cell and HG papillary histological subtype. In 0-2 cm vs. 2.1-4 cm RCCs, 13.8% vs. 20.2% individuals operated on harbored HG tumors and were more prevalent in males. Lower synchronous metastases rates were recorded in 0-2 cm RCC and ranged from 0 in respectively multilocular cystic to 0.9% in HG papillary histological subtype. The highest synchronous metastases rates were recorded in sarcomatoid dedifferentiation histological subtype (13.8% and 9.7%) in both groups.

Conclusions: Relative to 2.1-4 cm RCCs, 0-2 cm RCCs harbored lower rates of HG tumors, lower rates of aggressive variant histology and lower rates of synchronous metastases. The indications and demographics of patients selected for AS may be expanded in the future to include younger and healthier patients.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.003DOI Listing
April 2021

Metabolic syndrome predicts worse perioperative outcomes in patients treated with radical prostatectomy for non-metastatic prostate cancer.

Surg Oncol 2021 Jan 3;37:101519. Epub 2021 Jan 3.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Objectives: Metabolic syndrome (MetS) and its components (high blood pressure, BMI≥30, altered fasting glucose, low HDL cholesterol and high triglycerides) may undermine early perioperative outcomes after radical prostatectomy (RP). We tested this hypothesis.

Materials & Methods: Within the National Inpatient Sample database (2008-2015) we identified RP patients. The effect of MetS was tested in four separate univariable analyses, as well as in multivariable regression models predicting: 1) overall complications, 2) length of stay, 3) total hospital charges and 4) non-home based discharge. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics.

Results: Of 91,618 patients: 1) 50.2% had high blood pressure, 2) 8.0% had BMI≥30, 3) 13.0% had altered fasting glucose, 4) 22.8% had high triglycerides and 5) 0.03% had low HDL cholesterol. Respectively, one vs. two vs. three vs. four MetS components were recorded in 36.2% vs. 19.0% vs. 5.5% vs. 0.8% patients. Of all patients, 6.3% exhibited ≥3 components and qualified for MetS diagnosis. The rates of MetS increased over time (EAPC:+9.8%; p < 0.001). All four tested MetS components (high blood pressure, BMI≥30, altered fasting glucose and high triglycerides) achieved independent predictor status in all four examined endpoints. Moreover, a highly statistically significant dose-response was also confirmed for all four tested endpoints.

Conclusion: MetS and its components consistently and strongly predict early adverse outcomes after RP. Moreover, the strength of the effect was directly proportional to the number of MetS components exhibited by each individual patient, even if formal MetS diagnosis of ≥3 components has not been met.
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http://dx.doi.org/10.1016/j.suronc.2020.12.013DOI Listing
January 2021

Contemporary rates and predictors of open conversion during minimally invasive partial nephrectomy for kidney cancer.

Surg Oncol 2021 Mar 11;36:131-137. Epub 2020 Dec 11.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Objectives: To test contemporary rates and predictors of open conversion at minimally invasive partial nephrectomy (MIPN: laparoscopic or robotic partial nephrectomy).

Materials And Methods: Within the National Inpatient Sample database (2008-2015) we identified all MIPN patients and patients that underwent open conversion at MIPN. First, estimated annual percentage changes (EAPC) tested temporal trends of open conversion. Second, univariable and multivariable logistic regression models predicted open conversion at MIPN. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics.

Results: Of 7649 MIPN patients, 287 (3.8%) underwent open conversion. The rates of open conversion decreased over time (from 12 to 2.4%; EAPC: 24.8%; p = 0.004). In multivariable logistic regression models predicting open conversion, patient obesity achieved independent predictor status (OR:1.80; p < 0.001). Moreover, compared to high volume hospitals, medium volume (OR:1.48; p = 0.02) and low volume hospitals (OR:2.11; p < 0.001) were associated with higher rates of open conversion. Last but not least, when the effect of obesity was tested according to hospital volume, the rates of open conversion ranged from 2.2 (non obese patients treated at high volume hospitals) to 9.8% (obese patients treated at low volume hospitals).

Conclusion: Overall contemporary (2008-2015) rate of open conversion at MIPN was 3.8% and it was strongly associated with patient obesity and hospital surgical volume. In consequence, these two parameters should be taken into account during preoperative patients counselling, as well as in clinical and administrative decision making.
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http://dx.doi.org/10.1016/j.suronc.2020.12.004DOI Listing
March 2021

Upper Urinary Tract Tumors: Variant Histology Versus Urothelial Carcinoma.

Clin Genitourin Cancer 2020 Dec 2. Epub 2020 Dec 2.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Purpose: To evaluate stage at presentation and cancer-specific mortality (CSM) in upper urinary tract tumors according to histologic subtype.

Methods: Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), we identified patients with upper urinary tract tumors with pure variant histology (UTVH) and pure upper urinary tract urothelial carcinoma (UTUC). Cumulative incidence plots, after propensity score matching for tumor and patient characteristics, addressed CSM. Subgroup analyses addressed efficacy of radical nephroureterectomy (RNU) in stage T1-2 and of chemotherapy in metastatic UTVH patients.

Results: Of all 11,809 upper urinary tract tumor patients, 154 (1.3%) harbored squamous cell carcinoma (SCC), 86 (0.7%) adenocarcinoma, 39 (0.3%) neuroendocrine carcinoma, 38 (0.3%) other UTVH, and 11,492 (97.3%) UTUC. UTVH patients were more likely to exhibit metastatic stage disease at diagnosis than UTUC (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P < .01). After detailed matching for performance status, only SCC showed significantly higher CSM than UTUC (multivariate HR = 1.71; P < .01). Subgroup analyses in stage T1-2 RNU patients showed, relative to UTUC patients, no CSM differences for SCC or adenocarcinoma patients. No significant survival benefit for chemotherapy administration was identified in patients with metastatic SCC or metastatic adenocarcinoma. This study is limited by its sample size and the missing centralized pathologic review.

Conclusions: Disease stage at diagnosis is more advanced in UTVH patients than UTUC. Across all stages, CSM is higher for SCC than for UTUC. However, in T1-2 stage disease, RNU results in similar survival in SCC or adenocarcinoma versus UTUC.
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http://dx.doi.org/10.1016/j.clgc.2020.11.004DOI Listing
December 2020

The effect of race/ethnicity on histological subtype distribution, stage at presentation and cancer specific survival in urethral cancer.

Urol Oncol 2020 Dec 10. Epub 2020 Dec 10.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Objective: To test the effect of race/ethnicity on histological subtype, stage at presentation, and cancer specific mortality (CSM) in urethral cancer patients.

Material And Methods: Stratified analyses (Surveillance, Epidemiology and End Results [2004-2016]) tested the effect of race/ethnicity on histology and stage. Cumulative incidence-plots and multivariable competing-risks regression models (CRR), addressed CSM, after matching for TNM-stage, histology, age, and gender.

Results: Of 1,904 urethral cancer patients, 71% were Caucasian, 16% African American, 7% Hispanic and 5% other. African Americans were younger (66 years) than Caucasians (73 years) and Hispanics (74 years). In African Americans, adenocarcinoma (25%) and squamous cell carcinoma (SCC; 29%) were more frequent than in Caucasians (12% and 23%) or Hispanics (15% and 20%). African Americans with adenocarcinoma exhibited higher stage than other adenocarcinoma patients. In CRR, African Americans (35%) and Hispanics (29%) exhibited highest and second highest 3-year CSM, even after matching. After further multivariable adjustment of matched CRRs, CSM was higher in Hispanics (HR: 1.93, P= 0.03) and in African Americans (Hazard ratio 1.35, P= 0.07), relative to Caucasians.

Conclusion: Race/ethnicity impacts important differences on urethral cancer patients. African American race/ethnicity predisposes to higher rate of SCC and adenocarcinoma. Moreover, African Americans are younger and present with higher stage at diagnoses. Finally, even after most detailed matching for stage, age, gender, and adjustment for treatment and systemic therapy and socioeconomic status, African Americans and Hispanics exhibit higher CSM than Caucasians.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.031DOI Listing
December 2020

Incidence and Survival Rates of Contemporary Patients with Invasive Upper Tract Urothelial Carcinoma.

Eur Urol Oncol 2020 Dec 5. Epub 2020 Dec 5.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Contemporary incidence and mortality rates of upper tract urothelial carcinoma (UTUC) are unavailable.

Objective: To describe contemporary UTUC incidence and mortality rates in the USA.

Design, Setting, And Participants: Within the Surveillance, Epidemiology and End Results (SEER) database (2004-2016), we identified 13 075 UTUC patients. Of all, 9208 (70.4%) harbored nonmetastatic UTUC and were treated with radical nephroureterectomy versus 1174 (9.0%) who harbored metastatic UTUC.

Outcome Measurements And Statistical Analysis: Age-standardized incidence rates per 100 000 person years were calculated. Kaplan-Meier curves and multivariable Cox regression models addressed cancer-specific and overall mortality.

Results And Limitations: Overall UTUC age-standardized incidence rates decreased from 1.3 to 1.1 cases per 100 000 person years (average annual percentage change: -1.32%, p = 0.002). Moreover, age-standardized incidence rates decreased for TNM (average annual percentage change: -2.77%, p < 0.001) but increased for TNM stage (average annual percentage change: +2.87%, p < 0.01). In nonmetastatic UTUC treated with radical nephroureterectomy, stage, grade, age, and sex (p < 0.001) were independent predictors in multivariable Cox regression models focusing on cancer-specific mortality. In metastatic UTUC, chemotherapy administration, radical nephroureterectomy treatment, and ureteral primary were independent predictors of lower overall mortality in multivariable Cox regression models.

Conclusions: Although overall incidence of UTUC decreased, the incidence of metastatic UTUC increased over the study period. The majority of nonmetastatic UTUC harbored TNM stage. However, TNM, TNM, and TNM stages, respectively, affected 28.9%, 4.6%, and 10.0% of all incident cases. In metastatic UTUC, both chemotherapy and radical nephroureterectomy use exerted an important protective effect on overall mortality, and ureteral primaries exhibited more favorable survival.

Patient Summary: From 2004 to 2016, the incidence of upper tract urothelial carcinoma decreased in the USA. However, more advanced stages are on the rise.
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http://dx.doi.org/10.1016/j.euo.2020.11.005DOI Listing
December 2020

Bladder cancer stage and mortality: urban vs. rural residency.

Cancer Causes Control 2021 Feb 23;32(2):139-145. Epub 2020 Nov 23.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Objective: Relative to urban populations, rural patients may have more limited access to care, which may undermine timely bladder cancer (BCa) diagnosis and even survival.

Methods: We tested the effect of residency status (rural areas [RA < 2500 inhabitants] vs. urban clusters [UC ≥ 2500 inhabitants] vs. urbanized areas [UA, ≥50,000 inhabitants]) on BCa stage at presentation, as well as on cancer-specific mortality (CSM) and other cause mortality (OCM), according to the US Census Bureau definition. Multivariate competing risks regression (CRR) models were fitted after matching of RA or UC with UA in stage-stratified analyses.

Results: Of 222,330 patients, 3496 (1.6%) resided in RA, 25,462 (11.5%) in UC and 193,372 (87%) in UA. Age, tumor stage, radical cystectomy rates or chemotherapy use were comparable between RA, UC and UA (all p > 0.05). At 10 years, RA was associated with highest OCM followed by UC and UA (30.9% vs. 27.7% vs. 25.6%, p < 0.01). Similarly, CSM was also marginally higher in RA or UC vs. UA (20.0% vs. 20.1% vs. 18.8%, p = 0.01). In stage-stratified, fully matched CRR analyses, increased OCM and CSM only applied to stage T1 BCa patients.

Conclusion: We did not observe meaningful differences in access to treatment or stage distribution, according to residency status. However, RA and to a lesser extent UC residency status, were associated with higher OCM and marginally higher CSM in T1N0M0 patients. This observation should be further validated or refuted in additional epidemiological investigations.
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http://dx.doi.org/10.1007/s10552-020-01366-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810614PMC
February 2021

Impact of surgical wait times during summer months on the oncological outcomes following robotic-assisted radical prostatectomy: 10 years' experience from a large Canadian academic center.

World J Urol 2020 Oct 27. Epub 2020 Oct 27.

Department of Surgery, Division of Urology, Centre Hospitalier de L'université de Montréal (CHUM), Montreal, QC, Canada.

Purpose: Most Canadian hospitals face significant reductions in operating room access during the summer. We sought to assess the impact of longer wait times on the oncological outcomes of localized prostate cancer patients following robotic-assisted radical prostatectomy (RARP).

Methods: We conducted a retrospective review of a prospectively maintained RARP database in two high-volume academic centers, between 2010 and 2019. Assessed outcomes included the difference between post-biopsy UCSF-CAPRA and post-surgical CAPRA-S scores, Gleason score upgrade and biochemical recurrence rates (BCR). Multivariable regression analyses (MVA) were used to evaluate the effect of wait times.

Results: A total of 1057 men were included for analysis. Consistent over a 10 year period, summer months had the lowest surgical volumes despite above average booking volumes. The lowest surgical volume occurred during the month of July (7.1 cases on average), which was 35% less than the cohort average. The longest average wait times occurred for patients booked in June (93 ± 69 days, p < 0.001). On MVA, patients booked in June had significantly more chance of having an increase in CAPRA score [HR (95% CI) 1.64 (1.02-2.63); p = 0.04] and in CAPRA risk group [HR (95% CI) 1.82 (1.04-3.19); p = 0.03]. Cohort analysis showed fair correlation between CAPRA-score difference and wait time (Pearson correlation: r =  - 0.062; p = 0.044).

Conclusion: Our cohort results demonstrate that conventional RARP wait times are significantly and consistently prolonged during summer months over the past 10 years, with worse post-RARP oncological outcomes in terms of CAPRA scores. Other compensatory mechanisms to sustain consistent yearly operative output should be considered.
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http://dx.doi.org/10.1007/s00345-020-03496-2DOI Listing
October 2020

Prognostic value of preoperative albumin to globulin ratio in patients treated with salvage radical prostatectomy for radiation recurrent prostate cancer.

Minerva Urol Nefrol 2020 Sep 29. Epub 2020 Sep 29.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria -

Background: Serum albumin-to-globulin ratio (AGR) has been shown to be associated with poor prognosis in different malignancies. In this study we aimed to evaluate the predictive value of preoperative AGR for oncological outcomes in patients with radiation recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP).

Methods: A retrospective review of 214 consecutive patients with radiation-recurrent PCa who underwent SRP at five referral centers. Levels of albumin and globulin were obtained before SRP and used to calculate the preoperative AGR level. The optimal cut off value of preoperative AGR was 1.4. Univariable and multivariable Cox regression analyses were performed.

Results: Overall 89 (41.6%) patients had a low preoperative AGR. Low serum AGR was associated with biochemical recurrence (BCR) in univariable Cox regression analysis (HR 1.60, 95%CI 1.06-2.43, P=0.026). When adjusted for the effects of established preoperative and postoperative clinicopathologic confounders in different multivariable Cox regression models, this association did not retain its statistical significance. Moreover, preoperative AGR was not associated with metastasis free survival (P= 0.21), overall survival (P= 0.91) or cancer specific survival (P=0.61).

Conclusions: In patients with radiation recurrent PCa undergoing SRP, low preoperative AGR was associated with the risk of BCR only in univariable analysis. There was no association with metastasis or survival outcomes. Further studies are needed to evaluate this biomarker in the setting of primary PCa and to identify the patients most likely to benefit from a local therapy.
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http://dx.doi.org/10.23736/S0393-2249.20.03938-7DOI Listing
September 2020

Micropapillary Versus Urothelial Carcinoma of the Urinary Bladder: Stage at Presentation and Efficacy of Chemotherapy Across All Stages-A SEER-based Study.

Eur Urol Focus 2020 Sep 19. Epub 2020 Sep 19.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Stage-specific guideline recommendations are lacking for chemotherapy in micropapillary carcinoma of the urinary bladder (MCUB).

Objective: To test the efficacy of stage-specific chemotherapy for MCUB.

Design, Setting, And Participants: Within the Surveillance, Epidemiology and End Results (SEER) registry (2001-2016), we identified patients with MCUB and pure urothelial carcinoma of the urinary bladder (UCUB) of all stages.

Outcome Measurements And Statistical Analysis: Kaplan-Meier survival analyses and multivariate Cox regression models were used to determine cancer-specific mortality (CSM) in addition to power analyses.

Results And Limitations: Of 210 491 patients of all stages, 518 (0.2%) harboured MCUB versus 209 973 (99.8%) UCUB. Stage at presentation was invariably higher in MCUB than in UCUB patients. Of the MCUB patients, 223 (43.1%) received chemotherapy versus 42 921 (20.4%) of the UCUB patients. In MCUB patients, chemotherapy improved CSM-free survival significantly in metastatic stage (hazard ratio [HR] 0.36, p = 0.04). Longer median CSM-free survival was also associated with chemotherapy use in addition to radical cystectomy (RC) versus RC alone in non-organ-confined MCUB (HR 0.69, p = 0.2). Additional power analyses revealed an underpowered comparison. Finally, no CSM difference was recorded in organ-confined MCUB according to the use of chemotherapy in addition to RC versus RC alone (HR 0.98, p = 1).

Conclusions: Stage at presentation was invariably higher in MCUB than in UCUB patients. Very important CSM reduction was associated with chemotherapy use in metastatic MCUB. A promising protective effect of perioperative chemotherapy might also be applicable to non-organ-confined MCUB, but without sufficient statistical power. Conversely, no association was recorded in organ-confined MCUB.

Patient Summary: Patients with micropapillary carcinoma of the urinary bladder (MCUB) present in higher tumour stages than those with urothelial carcinoma of the urinary bladder. Chemotherapy for MCUB is effective in metastatic stages, but of no beneficial effect in organ-confined stage. In not-yet-metastatic but already non-organ-confined stages, we did not have enough observations to show a statistically significant protective effect of chemotherapy.
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http://dx.doi.org/10.1016/j.euf.2020.08.010DOI Listing
September 2020

Bladder Cancer: A Comparison Between Non-urothelial Variant Histology and Urothelial Carcinoma Across All Stages and Treatment Modalities.

Clin Genitourin Cancer 2021 Feb 18;19(1):60-68.e1. Epub 2020 Jul 18.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: The purpose of this study was to evaluate stage at presentation, treatment rates, and cancer-specific mortality (CSM) of non-urothelial variant histology (VH) bladder cancer (BCa) relative to urothelial carcinoma of the urinary bladder (UCUB).

Materials And Methods: Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), patients with VH BCa and UCUB were identified. Stage at presentation and treatment rates, as well as multivariably adjusted and matched CSM rates according to TNM stage within each histologic subtype, were reported.

Results: Of all 222,435 eligible patients with BCa, 11,147 (5.0%) harbored VH. Among those, squamous cell carcinoma accounted for 3666 (1.6%) patients, adenocarcinoma for 1862 (0.8%), neuroendocrine carcinoma for 1857 (0.8%), and other VH BCa for 3762 (1.7%) of the study cohort. Patients with VH BCa showed invariably more advanced TNM stage at presentation compared with patients with UCUB. Treatment rates according to TNM stages showed similar distribution of cystectomy rates in VH BCa and UCUB. However, important differences in the distribution of radiotherapy and chemotherapy rates existed within VH BCa and in comparison with UCUB. Furthermore, even after multivariable adjustment and matching with UCUB, squamous cell carcinoma exhibited higher CSM (hazard ratios, 1.43-1.95; all P < .01) across all stages. All other VH predominantly exhibited higher CSM than UCUB in either non-muscle-invasive or muscle-invasive nonmetastatic stages.

Conclusion: TNM stage at diagnosis is invariably more advanced in all patients with VH BCa versus patients with UCUB. Of all VH BCa, in multivariably adjusted stage for stage analyses, squamous cell carcinoma appears to have the worst natural history. All other VH subgroups exhibited more aggressive natural history than UCUB in nonmetastatic stages only.
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http://dx.doi.org/10.1016/j.clgc.2020.07.011DOI Listing
February 2021

Detectable Prostate-specific antigen value between 0.01 and 0.1 ng/ml following robotic-assisted radical prostatectomy (RARP): does it correlate with future biochemical recurrence?

World J Urol 2020 Jul 21. Epub 2020 Jul 21.

Division of Urology, Department of Surgery, Centre Hospitalier de l'université de Montréal (CHUM), 1000 Rue Saint-Denis, Montreal, QC, Canada.

Purpose: The aim of the study is to evaluate the impact of having a nadir and persistently detectable ultrasensitive prostate-specific antigen (uPSA) between 0.01 and 0.1 ng/ml post-robot-assisted radical prostatectomy (RARP), on future biochemical recurrence (BCR).

Methods: We conducted a retrospective analysis of a prospectively maintained cohort of 1359 men who underwent RARP, between 2006 and 2019. Patients were followed with uPSA at 1, 3, 6, 9, 12, 18, 24, 30, 36 months and annually thereafter. We included patients with PSA nadir values between 0.01 and 0.1 ng/ml within 6 months of surgery and with at least 2 follow-up measurements within the same range. We divided patients based on their BCR status and analyzed uPSA changes. Multivariable Cox-regression models (CRMs) were used to analyze variables predicting BCR-free survival (BCR-FS).

Results: We identified 167 (12.3%) patients for analyses, with a mean follow-up time of 60.2 ± 31.4 months. In our cohort, 5-year BCR-FS rate was 86%. Overall, 32 (19.1%) patients had BCR, with a mean time to BCR of 43.7 ± 24.3 months. BCR-free patients had stable mean uPSA values ≤ 0.033 ng/ml, while patients who developed BCR showed a slowly rising trend over time, with a significant difference between groups starting at 9 months (p < 0.02). In multivariable CRMs, a rising uPSA starting at 9 months was an independent predictor of BCR (HR: 2.7; 95% CI 1.6-3.82; p = 0.013).

Conclusion: In the present cohort, our results demonstrated that a considerable number of men have detectable uPSA values ranging between 0.01 and 0.1 ng/ml post-RARP. They can still be followed regularly to avoid patients' anxiety and salvage radiotherapy. Close follow-up is still required.
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http://dx.doi.org/10.1007/s00345-020-03367-wDOI Listing
July 2020

Obesity is associated with adverse short-term perioperative outcomes in patients treated with open and robot-assisted radical cystectomy for bladder cancer.

Urol Oncol 2021 01 17;39(1):75.e17-75.e25. Epub 2020 Jul 17.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Obese patients may be predisposed to adverse perioperative outcomes and it is uncertain whether robot-assisted radical cystectomy (RARC) benefits obese patients in comparison to open radical cystectomy (ORC). Thus, we tested the effect of obesity and surgical approach on perioperative outcomes and total hospital charges.

Methods: Within the National Inpatient Sample database (2008-2015), we identified obese (body mass index ≥30 kg/m2) vs. non-obese patients with non-metastatic bladder cancer treated with RARC or ORC. Estimated annual percent changes and weighted multivariable logistic and linear regression models adjusted for clustering as well as age, comorbidities, hospital volume, and respectively surgical approach, lengths of stay, and/or complications were used.

Results: Of all 11,594 patients (unweighted patient count), 1,119 (9.7%) were obese vs. 10,475 (90.3%) were not-obese. Obesity rate increased significantly over time (5.5%-13.3%, annual change: 11%, P = 0.001). RARC, as well as treatment in high volume hospitals was more prevalent in obese vs. non-obese patients (18.3 vs. 14.5% and 40.9 vs. 37.0%, both P < 0.01). In multivariable regression models, obesity independently predicted overall complications (odds ratio [OR] 1.23, confidence interval [CI]: 1.09-1.42), major complications (OR 1.63, CI: 1.41-1.87), longer hospital stay (OR 1.17, CI: 1.02-1.34) and higher total hospital charges ($+8,260, CI: 3951-12,570), all P < 0.01). In subgroup analyses in obese patients, RARC was not associated with overall (OR 1.15, P = 0.4) and major complications (OR 1.10, P = 0.6) or length of stay (OR 0.78, P = 0.1) compared with ORC but with higher hospital charges (+$16,794, P = 0.005).

Conclusion: Obesity predisposes to higher rates of adverse perioperative outcomes at radical cystectomy. The benefit of RARC could not be validated in obese patients.
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http://dx.doi.org/10.1016/j.urolonc.2020.06.020DOI Listing
January 2021

Bladder cancer incidence rates and trends in young adults aged 20-39 years.

Urol Oncol 2020 12 9;38(12):934.e11-934.e19. Epub 2020 Jul 9.

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada.

Objectives: To assess contemporary gender, race and stage-specific incidence and trends of bladder cancer among young adults in the United States.

Materials And Methods: Within Surveillance, Epidemiology, and End Results database (2001-2016), all patients aged 20 to 39 years-old with histologically confirmed bladder cancer were included. Age-standardized rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC).

Results: From 2000 to 2016, 2,772 new cases were recorded (ASR 0.2, AAPC -1.5%, P = 0.01). ASRs were higher in males than in females (0.3 and 0.1, respectively) and decreased significantly in both genders (AAPC -1.3, P = 0.02 and -2.2% P = 0.03, respectively). non-Hispanic White (NHW) accounted for 70.7% of the cohort and had the highest incidence (ASR 0.3) that decreased over time (AAPC -1.4%, P = 0.02). Conversely, ASRs in other ethnic groups were lower and showed stable trends. The most frequent tumor characteristics were Ta/TisN0M0 stage (71.0%, ASR 0.1, AAPC -1.0%, P = 0.1), low grade (61.6%, ASR 0.1, AAPC -4.3%, P = 0.001) and urothelial histology (95.5%, ASR 0.2, AAPC -1.5%, P = 0.01).

Conclusions: Despite the rarity of bladder cancer in those aged 20 to 39 years, a standard work-up is required to avoid advanced stage at diagnosis. The current data validate initial diagnoses at earliest stage in the vast majority of young adults. Moreover, decreasing ASRs in both genders are encouraging.
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http://dx.doi.org/10.1016/j.urolonc.2020.06.009DOI Listing
December 2020

Renal cell carcinoma incidence rates and trends in young adults aged 20-39 years.

Cancer Epidemiol 2020 08 22;67:101762. Epub 2020 Jun 22.

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: The burden of renal cell carcinoma (RCC) in young adults received marginal attention. We assessed contemporary gender, race and stage-specific incidence and trends of RCC among young adults (20-39 years-old) in the United States.

Methods: Within Surveillance, Epidemiology, and End Results database (2000-2016), patients aged 20-39 years with histologically confirmed RCC were included. Age-standardized incidence rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC).

Results: From 2000-2016, 7767 new RCC cases were recorded (ASR 0.6, AAPC  + 5.0 %, p < 0.001). ASRs were higher in males than in females (0.7 and 0.5, respectively) and increased significantly in both genders (AAPC + 5.0 % and +4.7 % both p < 0.001, respectively). Non-Hispanic American Indian/Alaska Native had the highest incidence (ASR 1.0) vs. non-Hispanic Asian or Pacific Islander the lowest (ASR 0.3). ASRs significantly increased in all ethnic groups. T1aN0M0 and T1bN0M0 stages showed the highest incidence and increase (ASR 0.3, AAPC + 5.9 %, p < 0.001 and ASR 0.1, AAPC + 5.7 %, p < 0.001, respectively). Also regional and distant stages increased (AAPC + 3.7 %, p = 0.001 and AAPC + 1.5 %, p = 0.06). The most frequent tumor characteristics were G2 (44.4 %, ASR 0.3, AAPC + 6.3 %, p < 0.001) and G1 (13.1 %, ASR 0.1, AAPC + 1.1 %, p = 0.2), as well as clear cell histology (54.8 %, ASR 0.3, AAPC  + 7.6 %, p < 0.001).

Conclusions: RCC in young adults is rare, but increasing. This is mainly due to T1aN0M0 tumors. Nonetheless, also regional diseases are significantly increasing. Differences between ethnic groups exist and may warrant further research.
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http://dx.doi.org/10.1016/j.canep.2020.101762DOI Listing
August 2020

PSA, stage, grade and prostate cancer specific mortality in Asian American patients relative to Caucasians according to the United States Census Bureau race definitions.

World J Urol 2021 Mar 26;39(3):787-796. Epub 2020 May 26.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: The United States Census Bureau recommends distinguishing between "Asians" vs. "Native Hawaiians or Other Pacific Islanders" (NHOPI). We tested for prognostic differences according to this stratification in patients with prostate cancer (PCa) of all stages.

Methods: Descriptive statistics, time-trend analyses, Kaplan-Meier plots and multivariate Cox regression models were used to test for differences at diagnosis, as well as for cancer specific mortality (CSM) according to the Census Bureau's definition in either non-metastatic or metastatic patients vs. 1:4 propensity score (PS)-matched Caucasian controls, identified within the Surveillance, Epidemiology and End Results database (2004-2016).

Results: Of all 380,705 PCa patients, NHOPI accounted for 1877 (0.5%) vs. 23,343 (6.1%) remaining Asians vs. 93.4% Caucasians. NHOPI invariably harbored worse PCa characteristics at diagnosis. The rates of PSA ≥ 20 ng/ml, Gleason ≥ 8, T3/T4, N1- and M1 stages were highest for NHOPI, followed by Asians, followed by Caucasians (PSA ≥ 20: 18.4 vs. 14.8 vs. 10.2%, Gleason ≥ 8: 24.9 vs. 22.1, vs. 15.9%, T3/T4: 5.5 vs. 4.2 vs. 3.5%, N1: 4.4 vs. 2.8, vs. 2.7%, M1: 8.3 vs. 4.9 vs. 3.9%). Despite the worst PCa characteristics at diagnosis, NHOPI did not exhibit worse CSM than Caucasians. Moreover, despite worse PCa characteristics, Asians exhibited more favorable CSM than Caucasians in comparisons that focussed on non-metastatic and on metastatic patients.

Conclusions: Our observations corroborate the validity of the distinction between NHOPI and Asian patients according to the Census Bureau's recommendation, since these two groups show differences in PSA, grade and stage characteristics at diagnosis in addition to exhibiting differences in CSM even after PS matching and multivariate adjustment.
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http://dx.doi.org/10.1007/s00345-020-03242-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969699PMC
March 2021

Radical cystectomy improves survival in patients with stage T1 squamous cell carcinoma and neuroendocrine carcinoma of the urinary bladder.

Eur J Surg Oncol 2021 02 12;47(2):463-469. Epub 2020 May 12.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Background: Radical cystectomy (RC) is often performed for T1 variant histology bladder cancer (VHBC), based on weak clinical evidence. We tested for cancer specific survival (CSS) differences after RC between T1 VHBC vs. urothelial carcinoma of the urinary bladder (UBC).

Methods: Within the Surveillance, Epidemiology and End Results registry (SEER, 2001-2016), we retrospectively identified T1N0M0 VHBC (adenocarcinoma, squamous cell carcinoma [SqCC], neuroendocrine carcinoma and other VHBC) and UBC patients. Kaplan-Meier plots, multivariate Cox regression models (CRM) with inverse probability treatment weighting (IPTW) and competing risks regression (CRR) tested CSS rates after RC in stage T1 vs. no-RC according to VHBC type and UBC.

Results: Of all 37,528 T1N0M0 bladder cancer patients, 1726 (4.6%) harboured VHBC. Of those, 598 (1.6%) had SqCC, 409 (1.1%) adenocarcinoma, 249 (0.7%) neuroendocrine carcinoma and 470 (1.3%) other VHBC. RC was performed in 7.4-11.0% of VHBC vs. 5.1% of high grade UBC patients. In patients with neuroendocrine and SqCC, RC was associated with higher CSS rates than any other surgical treatment modality (both p ≤ 0.01). Sixty-month CSS was 100% vs. 67% in neuroendocrine and 86% vs. 66% in SqCC in unadjusted analyses and remained statistically significantly higher in multivariate, IPTW adjusted analyses and in multivariate CRR. No difference was recorded for adenocarcinoma or other VHBC types.

Conclusions: RC for stage T1N0M0 VHBC appears to provide a protective effect with respect to CSS in patients with SqCC and neuroendocrine carcinoma, but not in adenocarcinoma or other VHBC.
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http://dx.doi.org/10.1016/j.ejso.2020.05.006DOI Listing
February 2021

Renal Cell Carcinoma: Comparison between Variant Histology and Clear Cell Carcinoma across All Stages and Treatment Modalities.

J Urol 2020 10 6;204(4):671-676. Epub 2020 Apr 6.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.

Purpose: We evaluated stage at presentation and cancer specific mortality according to variant histology relative to clear cell renal cell carcinoma.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016) we identified variant histology and clear cell renal cell carcinoma cases. Cumulative incidence plots, multivariate Cox regression models matched for stage, grade and other patient characteristics addressed cancer specific mortality. Subgroup analyses relied on inverse probability treatment weighting according to nephrectomy type.

Results: Of all 69,785 patients with renal cell carcinoma 2,495 harbored variant histology (3.6%). Of patients with variant histology 70.1% (1,748) harbored sarcomatoid vs 11.2% (280) collecting duct vs 7.6% (190) mesenchymal vs 3.8% (94) neuroendocrine vs 2.9% (72) renal medullary vs 2.5% (62) mucinous tubular and spindle cell, and 2.0% (49) rhabdoid tumors. All patients with variant histology exhibited more advanced TNM stage at diagnosis than clear cell renal cell carcinoma, except for mucinous tubular and spindle cell. After matching with G4 clear cell renal cell carcinoma, collecting duct (multivariate HR 1.6, p <0.01), sarcomatoid (HR 1.8, p <0.01), renal medullary (HR 1.7, p=0.1) and rhabdoid variant histology (HR 1.5, p=0.1) showed higher cancer specific mortality than clear cell renal cell carcinoma. No cancer specific mortality differences were recorded for mesenchymal, neuroendocrine and mucinous tubular and spindle cell variant histology. In nephrectomy subgroup higher cancer specific mortality was recorded after partial nephrectomy than radical nephrectomy in sarcomatoid variant histology after inverse probability treatment weighting and multivariate adjustment (HR 1.2, p=0.02).

Conclusions: TNM stage at diagnosis is universally more advanced in patients with variant histology, except for mucinous tubular and spindle cell. Cancer specific mortality is higher in collecting duct, sarcomatoid, rhabdoid and renal medullary variant histology, but not in other variant histology. Partial nephrectomy is associated with worse survival in sarcomatoid variant histology but could not be assessed in other variant histology due to small sample size.
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http://dx.doi.org/10.1097/JU.0000000000001063DOI Listing
October 2020

Contemporary Rates and Predictors of Open Conversion During Minimally Invasive Radical Prostatectomy for Nonmetastatic Prostate Cancer.

J Endourol 2020 05 14;34(5):600-607. Epub 2020 Apr 14.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

To test contemporary rates and predictors of open conversion at minimally invasive (laparoscopic or robotic) radical prostatectomy (MIRP). Within the National Inpatient Sample database (2008-2015), we identified all MIRP patients and patients who underwent open conversion at MIRP. First, estimated annual percentage changes (EAPCs) tested temporal trends of open conversion. Second, multivariable logistic regression models predicted open conversion at MIRP. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. Of 57,078 MIRP patients, 368 (0.6%) underwent open conversion. The rates of open conversion decreased over time (from 1.80% to 0.38%; EAPC: -26.0%;  = 0.003). In multivariable logistic regression models predicting open conversion, patient obesity (odds ratio [OR]: 2.10;  < 0.001), frailty (OR: 1.45;  = 0.005), and Charlson comorbidity index (CCI) ≥2 (OR: 1.57;  = 0.03) achieved independent predictor status. Moreover, compared with high-volume hospitals, medium-volume (OR: 2.03;  < 0.001) and low-volume hospitals (OR: 3.86;  < 0.001) were associated with higher rates of open conversion. Last but not least, when the interaction between the number of patient risk factors (obesity and/or frailty and/or CCI ≥2) and hospital volume was tested, a dose-response effect was observed. Specifically, the rates of open conversion ranged from 0.3% (patients with zero risk factors treated at high-volume hospitals) to 2.2% (patients with two to three risk factors treated at low-volume hospitals). Overall contemporary (2008-2015) rate of open conversion at MIRP was 0.6% and it was strongly associated with patient obesity, frailty, CCI ≥2, and hospital surgical volume. In consequence, these parameters should be taken into account during preoperative patients counseling, as well as in clinical and administrative decision making.
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http://dx.doi.org/10.1089/end.2020.0074DOI Listing
May 2020

Metabolic Syndrome Predicts Worse Perioperative Outcomes in Patients Treated With Partial Nephrectomy for Renal Cell Carcinoma.

Urology 2020 Jun 6;140:91-97. Epub 2020 Mar 6.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Objective: To test the association between metabolic syndrome (MetS) and its components (high blood pressure, body mass index [BMI]  ≥ 30, altered fasting glucose, low high-density lipoprotein cholesterol and high triglycerides) on perioperative outcomes after partial nephrectomy (PN).

Methods: Within the National Inpatient Sample database (2000-2015) we identified all PN patients. First, temporal trends of MetS were reported. Second, the effect of MetS components was tested in multivariable logistic regression models predicting overall and specific perioperative complications. Third, we tested for dose-response from the concomitant effect of multiple MetS components. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics.

Results: Of 25,875 patients: (1) 59.3% had high blood pressure, (2) 14.7% had BMI  ≥ 30, (3) 21.7% had altered fasting glucose, (4) 20.2% had high triglycerides, and (5) <0.01% had low high-density lipoprotein cholesterol. One vs 2 vs 3 vs 4 MetS components were recorded in 34.9% vs 22.9% vs 8.9% vs 2.2% patients. Of all, 11.1% exhibited  ≥ 3 components and qualified for MetS. The rates of MetS increased over time (estimated annual percentage changes: +12.0%;P <.001). The 4 tested MetS components (high blood pressure, BMI  ≥ 30, altered fasting glucose, and high triglycerides) achieved independent predictor status in multivariable models predicting overall, cardiac, miscellaneous medical, vascular, and respiratory complications, as well as transfusions. Moreover, a statistically significant dose-response was confirmed for the same endpoints.

Conclusion: MetS and its components consistently and strongly predict perioperative complications after PN. Moreover, the strength of the effect was directly proportional to the number of MetS components exhibited by each individual patient, even if formal MetS diagnosis of  ≥ 3 components has not been met.
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http://dx.doi.org/10.1016/j.urology.2020.02.019DOI Listing
June 2020