Publications by authors named "Lara Franziska Stolzenbach"

18 Publications

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Editorial Comment.

J Urol 2021 Apr 6:101097JU000000000000169502. Epub 2021 Apr 6.

Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland.

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http://dx.doi.org/10.1097/JU.0000000000001695.02DOI Listing
April 2021

Sex- and Age-Related Differences in the Distribution of Metastases in Patients With Upper Urinary Tract Urothelial Carcinoma.

J Natl Compr Canc Netw 2021 Feb 11:1-7. Epub 2021 Feb 11.

1Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC.

Materials And Methods: Within the Nationwide Inpatient Sample database (2000-2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64-72, 73-79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests.

Results: Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women).

Conclusions: Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.
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http://dx.doi.org/10.6004/jnccn.2020.7637DOI Listing
February 2021

Sex- and age-related differences in the distribution of bladder cancer metastases.

Jpn J Clin Oncol 2021 Feb 9. Epub 2021 Feb 9.

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

Objective: Our objective was to investigate age- and sex-related differences in the distribution of metastases in patients with metastatic bladder cancer.

Methods: Within the National Inpatient Sample database (2008-2015), we identified 7040 patients with metastatic bladder cancer. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex.

Results: Of 7040 patients with metastatic bladder cancer, 5226 (74.2%) were men and 1814 (25.8%) were women. Thoracic, abdominal, bone and brain metastases were present in 19.5 vs. 23.0%, 43.6 vs. 46.9%, 23.9 vs. 18.7% and 2.4 vs. 2.9% of men vs. women, respectively. Bone was the most common metastatic site in men (23.9%) vs. lung in women (22.4%). Increasing age was associated with decreasing rates of abdominal (from 44.9 to 40.2%) and brain (from 3.2 to 1.4%) metastases in men vs. decreasing rates of bone (from 21.0 to 13.3%) and brain (from 5.1 to 2.0%) metastases in women (all P < 0.05). Finally, rates of metastases in multiple organs also decreased with age, in both men and women.

Conclusions: The distribution of metastases in bladder cancer varies according to sex. Moreover, differences exist according to patient age and these differences are also sex-specific. In consequence, patient age and sex should be considered in the interpretation of imaging, especially when findings are indeterminate.
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http://dx.doi.org/10.1093/jjco/hyaa273DOI Listing
February 2021

Racial differences in the distribution of bladder cancer metastases: a population-based analysis.

Cent European J Urol 2020 31;73(4):407-415. Epub 2020 Oct 31.

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

Introduction: Bladder cancer is the second most common genitourinary malignancy in the United States. The incidence of bladder cancer rises with age, and it is two times more common in Caucasians than in African-Americans (23.1 vs. 12.6 cases/100,000 persons). We aimed to investigate the racial and age-related differences in the distribution of metastasis in a large, contemporary cohort of metastatic bladder cancer patients.

Material And Methods: Within the National Inpatient Sample database (2008-2015) we identified 5,767 patients with metastatic bladder cancer. Trend test, Chi-square test and multivariable logistic regression models were used to evaluate the relationship between ethnicity, age, and site of metastasis.

Results: Of 5,767 patients with metastatic bladder cancer, 598 (10.4%) were African-American. Lung was the most common metastatic site in African-Americans (28.6%) vs. bone in Caucasians (21.7%). Overall, African-Americans showed higher rates of lung (+10.2%), liver (+7.5%) and bone (+5.2%) metastases, compared to Caucasians (all p <0.01). Brain metastases were rare in both ethnicities (3.3 vs. 2.4%; p = 0.2). Rates of exclusive bone, lung or liver metastases increased with age, but were higher in African-Americans, regardless of age strata. In the multivariable logistic regression models, African-American ethnicity independently predicted higher risk of lung (Odds ratio: 1.69), liver (odds ratio: 1.50) and bone (odds ratio: 1.27) metastases, relative to Caucasians. Moreover, a dose-response effect was found after combining the three main risk factors for developing bone metastases, namely African-American ethnicity, younger age and male gender.

Conclusions: Racial differences exist in the distribution of metastatic bladder cancer metastasis. Moreover, based on higher risk of bone metastases in African-American patients, bone imaging may be warranted in this patient population, especially in the presence of other risk factors for bone metastases, namely male gender or younger age.
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http://dx.doi.org/10.5173/ceju.2020.0269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848828PMC
October 2020

The impact of sex and age on distribution of metastases in patients with renal cell carcinoma.

Int J Clin Oncol 2021 Jan 30. Epub 2021 Jan 30.

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

Background: Our objective was to investigate age and sex-related discrepancies on distribution of metastases in patients with metastatic renal cell carcinoma (RCC).

Methods: Within the National Inpatient Sample database (2008-2015) we identified 9607 patients with metastatic RCC. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex.

Results: Of 9607 patients with metastatic RCC, 6344 (65.9%) were men and 3263 (34.1%) were women. Thoracic, abdominal, bone and brain metastases were present in 51.1 vs. 52.8%, 42.6 vs. 44.3%, 29.9 vs. 29.2% and 8.6 vs. 8.8% of men vs. women, respectively. Increasing age was associated with decreasing rates of thoracic (from 55.5 to 48.5%) and brain (from 8.6 to 5.8%) metastases in men and with decreasing rates of abdominal (from 48.3 to 39.6%), bone (from 32.6 to 24.9%) and brain (from 8.8 to 5.4%) metastases in women. (all p < 0.05). Rates of concomitant metastatic sites also decreased with increasing age, from 57.1 to 50.8% in men and from 54.1 to 50.2% in women.

Conclusions: Important age and sex-related differences exist in the distribution of RCC metastases. The distribution of metastases is marginally different between sexes. Specifically, more advanced age is associated with lower rates of thoracic and brain metastases in men and with lower rates of abdominal, bone and brain metastases in women. Age and sex should be take into consideration into the staging management strategy, as well as into the follow-up strategy of patients with metastatic RCC.
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http://dx.doi.org/10.1007/s10147-021-01874-3DOI Listing
January 2021

Improving the Stratification of Patients With Intermediate-risk Prostate Cancer.

Clin Genitourin Cancer 2020 Nov 10. Epub 2020 Nov 10.

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

Background: Intermediate-risk prostate cancer (IR PCa) phenotypes may vary from favorable to unfavorable. National Comprehensive Cancer Network (NCCN) criteria help distinguish between those groups. We studied and attempted to improve this stratification.

Patients And Methods: A total of 4048 (NCCN favorable: 2015 [49.8%] vs. unfavorable 2033 [50.2%]) patients with IR PCa treated with radical prostatectomy were abstracted from an institutional database (2000-2018). Multivariable logistic regression models predicting upstaging and/or upgrading (Gleason Grade Group [GGG] IV-V and/or ≥ pT3 or pN1) in IR PCa were developed, validated, and directly compared with the NCCN IR PCa stratification.

Results: All 4048 patients were randomly divided between development (n = 2024; 50.0%) and validation cohorts (n = 2024; 50.0%). The development cohort was used to fit basic (age, prostate-specific antigen, clinical T stage, biopsy GGG, and percentage of positive cores [all P < .001]) and extended models (age, prostate-specific antigen, clinical T stage, biopsy GGG, prostate volume, and percentage of tumor within all biopsy cores [all P < .001]). In the validation cohort, the basic and the extended models were, respectively, 71.4% and 74.7% accurate in predicting upstaging and/or upgrading versus 66.8% for the NCCN IR PCa stratification. Both models outperformed NCCN IR PCa stratification in calibration and decision curve analyses (DCA). Use of NCCN IR PCa stratification would have misclassified 20.1% of patients with ≥ pT3 or pN1 and/or GGG IV to V versus 18.3% and 16.4% who were misclassified using the basic or the extended model, respectively.

Conclusion: Both newly developed and validated models better discriminate upstaging and/or upgrading risk than the NCCN IR PCa stratification.
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http://dx.doi.org/10.1016/j.clgc.2020.11.003DOI Listing
November 2020

External beam radiation therapy improves survival in elderly metastatic prostate cancer patients with low PSA.

Urol Oncol 2021 02 11;39(2):131.e1-131.e7. Epub 2020 Nov 11.

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

Background: It is unknown, whether metastatic prostate cancer (CaP) patients with intermediate life expectancy (5-10 years) should be considered for external beam radiation therapy (EBRT) to the prostate. We addressed this void.

Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 835 M1a or M1b CaP substaged patients with prostate-specific antigen (PSA) < 20 ng/ml and with intermediate life expectancy (LE) 5 to 10 years, treated with EBRT or no EBRT. Inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots and Cox-regression models (CRMs) were used.

Results: Overall, 179 (21.4%) patients received EBRT and 656 (78.6%) did not. EBRT rates increased from 13.9 to 23.8% (2004-2016; P= 0.04). After IPTW-adjustment, median OS was 45 vs. 35 months, in EBRT vs. no EBRT patients (P < 0.001). In IPTW-adjusted Cox-regression models, EBRT independently predicted lower overall mortality (hazard ratio [HR]: 0.7, CI 0.61-0.89; P= 0.001). After stratification according to M1 substages, EBRT was associated with lower overall mortality in M1a (HR: 0.2, CI 0.05-0.91; P= 0.03) and M1b (HR: 0.7, CI 0.55-0.88; P = 0.003) substages.

Conclusion: EBRT was associated with lower mortality in metastatic CaP patients with low PSA and intermediate LE (5-10 years). In consequence, greater consideration for EBRT should be given in those patients. However, it is important to consider study limitations until clinical trials confirm the proposed benefit.
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http://dx.doi.org/10.1016/j.urolonc.2020.10.011DOI Listing
February 2021

Prognostic factors in patients with small renal masses: a comparison between <2 vs. 2.1-4 cm renal cell carcinomas.

Cancer Causes Control 2021 Feb 9;32(2):119-126. Epub 2020 Nov 9.

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

Background: Few data factually support the prognostic distinction between renal cell carcinomas (RCC) < 2 vs. 2.1-4 cm, in terms of cancer-specific mortality (CSM). We investigated CSM rates over time in <2 vs. 2.1-4 cm RCC, according to patient and tumor characteristics.

Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, we focused on patients with TNM RCC who underwent either radical or partial nephrectomy between 2000 and 2015. Temporal trends, Kaplan-Meier plots and multivariable Cox-regression analyses assessed CSM.

Results: Of 43,147 TNM patients, 12,238 (28.4%) harbored RCC < 2 cm and 30,909 (71.6%) 2.1-4 cm RCC. The distribution of histological subtypes according to 2 cm cut-off was as follows: a). clear-cell G1/G2: 64.5 vs. 61.8%; b). papillary G1/G2 15.9 vs. 11.1%; c). clear-cell G3/G4: 9.9 vs. 16.1%; d). papillary G3/G4 4.9 vs. 5.4%; and e). chromophobe 4.9 vs. 5.2%. Five-year CSM rates were invariably lower in RCC < 2 cm than in 2.1-4 cm, for all histological subtypes and grade groups (a-e), even after additional multivariable adjustment for age and residual tumor size differences. 5-year CSM rates improved in more contemporary years, in both tumor size groups (< 2 vs. 2.1-4 cm), but to a greater extent in 2.1-4 cm renal masses.

Conclusion: Our results validate the presence of prognostically more favorable CSM outcomes in RCC < 2 cm vs. 2.1-4 cm, across all histological subtypes and grades. Moreover, temporal improvements were also recorded in both <2 and 2.1-4 cm RCC groups, with more pronounced improvements in patients with 2.1-4 cm renal masses. However, prospective randomized trials are needed to further confirm our results.
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http://dx.doi.org/10.1007/s10552-020-01364-3DOI Listing
February 2021

Differences between rural and urban prostate cancer patients.

World J Urol 2020 Nov 5. Epub 2020 Nov 5.

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

Background: We hypothesized that the residency status (rural area [RA] vs urban clusters [UC] vs urban areas [UA]) affects stage and cancer-specific mortality (CSM) in contemporary newly diagnosed prostate cancer (PCa) patients of all stages, regardless of treatment.

Methods: Newly diagnosed PCa patients with available residency status were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Propensity-score (PS) matching, cumulative incidence plots, multivariate competing-risks regression (CRR) models were used.

Results: Of 531,468 PCa patients of all stages, 6653 (1.3%) resided in RA, 50,932 (9.6%) in UC and 473,883 (89.2%) in UA. No statistically significant or clinically meaningful differences in stage at presentation or CSM were recorded. Conversely, 10-year other cause-mortality (OCM) rates were 27.2% vs 23.7% vs 18.9% (p < 0.001) in RA vs UC vs UA patients, respectively. In CRR models, RA (subhazard ratio [SHR] 1.38; p < 0.001) and UC (SHR 1.18; p < 0.001) were independent predictors for higher OCM relative to UA. These differences remained statistically significant in fully PS-adjusted multivariate CRR models.

Conclusion: RA, and to a lesser extent UC, PCa patients are at higher risk of OCM than UA patients. Higher OCM may indicate shorter life expectancy and should be considered in treatment decision making.
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http://dx.doi.org/10.1007/s00345-020-03483-7DOI Listing
November 2020

Prostate Cancer Grade and Stage Misclassification in Active Surveillance Candidates: Black Versus White Patients.

J Natl Compr Canc Netw 2020 11 2;18(11):1492-1499. Epub 2020 Nov 2.

1Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: Misclassification rates defined as upgrading, upstaging, and upgrading and/or upstaging have not been tested in contemporary Black patients relative to White patients who fulfilled criteria for very-low-risk, low-risk, or favorable intermediate-risk prostate cancer. This study aimed to address this void.

Methods: Within the SEER database (2010-2015), we focused on patients with very low, low, and favorable intermediate risk for prostate cancer who underwent radical prostatectomy and had available stage and grade information. Descriptive analyses, temporal trend analyses, and multivariate logistic regression analyses were used.

Results: Overall, 4,704 patients with very low risk (701 Black vs 4,003 White), 17,785 with low risk (2,696 Black vs 15,089 White), and 11,040 with favorable intermediate risk (1,693 Black vs 9,347 White) were identified. Rates of upgrading and/or upstaging in Black versus White patients were respectively 42.1% versus 37.7% (absolute Δ = +4.4%; P<.001) in those with very low risk, 48.6% versus 46.0% (absolute Δ = +2.6%; P<.001) in those with low risk, and 33.8% versus 35.3% (absolute Δ = -1.5%; P=.05) in those with favorable intermediate risk.

Conclusions: Rates of misclassification were particularly elevated in patients with very low risk and low risk, regardless of race, and ranged from 33.8% to 48.6%. Recalibration of very-low-, low-, and, to a lesser extent, favorable intermediate-risk active surveillance criteria may be required. Finally, our data indicate that Black patients may be given the same consideration as White patients when active surveillance is an option. However, further validations should ideally follow.
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http://dx.doi.org/10.6004/jnccn.2020.7580DOI Listing
November 2020

Oncological outcomes of pathologically organ-confined, lymph node-positive prostate cancer after radical prostatectomy.

Urol Oncol 2021 Apr 20;39(4):234.e1-234.e7. Epub 2020 Oct 20.

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Background: The aim of this study was to investigate the impact of lymph-node involvement on oncological outcomes in patients with pathologically organ-confined prostate cancer (pT2 CaP) after radical prostatectomy (RP).

Methods: We retrospectively analyzed 9,631 pT2 CaP patients who underwent RP at a single institution between 1998 and 2018. Kaplan-Meier plots and Cox regression models (CRMs) assessed biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS) according to N-stage. In subgroup analyses of N1 patients, Kaplan-Meier plots and CRMs were stratified according to adjuvant treatment.

Results: Of 9,631 pT2 staged patients, 241 (2.5%) harbored lymph-node metastases after RP (pN1). The median follow-up was 60.8 months. No pT2 N1-staged patient died due to CaP. The 5-year BCR-free survival rates were 54.7 vs. 88.4% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). The 5-year MFS rates were 92.5 vs. 98.9% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). Within pT2 N1 patients, presence of ≥3 positive lymph nodes was an independent risk factor for BCR (hazard ratio [HR] 3.4, P < 0.001) and for metastatic progression (HR 1.7, P = 0.04). Finally, 3-year BCR-free survival was improved in pT2 N1 patients treated with adjuvant radiation therapy (87.1% vs. 63.7% for patients who received other treatment options [P < 0.001]).

Conclusion: Patients with pathologically organ-confined but lymph node-positive CaP exhibited favorable oncological outcomes after RP. Presence of ≥3 positive LNs predicted higher rates of BCR and metastatic progression. In consequence, in pT2 N1 patients treated with RP with ≥3 positive LNs, adjuvant treatment may be considered.9.
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http://dx.doi.org/10.1016/j.urolonc.2020.10.010DOI Listing
April 2021

The effect of sex on disease stage and survival after radical cystectomy: a population-based analysis.

Urol Oncol 2021 Apr 6;39(4):236.e1-236.e7. Epub 2020 Oct 6.

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

Background: The increased awareness regarding the sex gap in bladder cancer (BCa) care over the last decade may have resulted in more timely-wise referral patterns and treatment of female patients with BCa. Thus, we tested the association of sex with disease stage at presentation, as well as with cancer-specific mortality (CSM) after radical cystectomy (RC) in a contemporary cohort of patients with nonmetastatic urothelial bladder cancer (UCUB).

Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 14,086 patients (10,879 men and 3,207 women) treated with RC for non-metastatic UCUB. Temporal trend, interaction analyses, logistic regression, cumulative incidence, and competing-risks regression analyses were used.

Results: Overall, 10,879 (77.2%) men and 3,207 (22.8%) women underwent RC between 2004 and 2016. Female gender was an independent predictor of non-organ-confined (NOC) UCUB at RC in multivariable analyses (odds ratio: 1.23; 95% confidence intervals [CI] 1.10-1.38; P < 0.001). While NOC rates in men decreased over time (from 54.8% to 45.7%; P < 0.01), NOC rates in women remained stationary (from 60.6% to 57.3%; P = 0.15) and the excess NOC rate between men and women increased from + 5.8% in 2004 to +11.6% in 2016. Moreover, in multivariable analyses adjusted for other covariates, female gender was an independent predictor of higher CSM after RC in NOC UCUB (HR: 1.14; 95%CI 1.04-1.24; P < 0.01), but not in localized UCUB (P = 0.06).

Conclusion: It is worrisome that, while in men the rate of NOC is decreasing, NOC rates in females have not improved over time. Moreover, it is also worrisome that, despite adjustment for both pathological tumor and patient characteristics, female sex remains an adverse prognostic factor for CSM. Reassessment of referral, diagnostic, and treatment patterns aimed at eliminating these sex discrepancies appears warranted.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.004DOI Listing
April 2021

Comparison of Mexican-American vs Caucasian prostate cancer active surveillance candidates.

Urol Oncol 2021 01 17;39(1):74.e1-74.e7. Epub 2020 Sep 17.

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

Background: We compared upgrading and upstaging rates in low risk and favorable intermediate risk prostate cancer (CaP) patients according to racial and/or ethnic group: Mexican-Americans and Caucasians.

Methods: Within Surveillance, Epidemiology and End Results database (2010-2015), we identified low risk and favorable intermediate risk CaP patients according to National Comprehensive Cancer Network guidelines. Descriptives and logistic regression models were used. Furthermore, a subgroup analysis was performed to test the association between Mexican-American vs. Caucasian racial and/or ethnic groups and upgrading either to Gleason-Grade Group (GGG II) or to GGG III, IV or V, in low risk or favorable intermediate risk CaP patients, respectively.

Results: We identified 673 (2.6%) Mexican-American and 24,959 (97.4%) Caucasian CaP patients. Of those, 14,789 were low risk (434 [2.9%] Mexican-Americans vs. 14,355 [97.1%] Caucasians) and 10,834 were favorable intermediate risk (239 [2.2%] Mexican-Americans vs. 10,604 [97.8%] Caucasians). In low risk CaP patients, Mexican-American vs. Caucasian racial and/or ethnic group did not result in either upgrading or upstaging differences. However, in favorable intermediate risk CaP patients, upgrading rate was higher in Mexican-Americans than in Caucasians (31.4 vs. 25.5%, OR 1.33, P = 0.044), but no difference was recorded for upstaging. When comparisons focused on upgrading to GGG III, IV or V, higher rate was recorded in Mexican-American relative to Caucasian favorable intermediate risk CaP patients (20.4 vs. 15.4%, OR 1.41, P = 0.034).

Conclusion: Low risk Mexican-American CaP patients do not differ from low risk Caucasian CaP patients. However, favorable intermediate risk Mexican-American CaP patients exhibit higher rates of upgrading than their Caucasian counterparts. This information should be considered at treatment decision making.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.012DOI Listing
January 2021

External beam radiation therapy improves survival in low-volume metastatic prostate cancer patients: a North American population-based study.

Prostate Cancer Prostatic Dis 2021 Mar 1;24(1):253-260. Epub 2020 Sep 1.

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

Background: We hypothesized that the survival benefit of external beam radiation therapy (EBRT) recorded in European low-volume metastatic prostate cancer (mPCA) patients, will apply to similar North American patients.

Methods: Newly diagnosed mPCa patients with M1a/b substages, treated with EBRT or no EBRT were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Kaplan-Meier plots and Cox-regression models targeted overall mortality (OM) and cancer specific-mortality (CSM) according to EBRT administration. M1 substages and PSA stratified analyses were performed. Internal validation relied on 2000 bootstrap resamples.

Results: Of 15,494 patients, 1156 (7.5%) were M1a vs 14,338 (92.5%) were M1b. PSA at diagnosis ≤10.0 ng/ml was recorded in 1463 (9.4%) patients. In all 15,494 patients, EBRT did not affect OM (hazard ratio [HR] 1.0; p = 0.5). However, in M1a patients and M1b patients with PSA ≤ 10.0 ng/ml EBRT was associated with lower OM (HR 0.73, CI 0.62-0.86; p < 0.001) but not in M1b patients with PSA > 10.0 ng/ml. The PSA cut-off of ≤ 10.0 ng/ml represented the most statistically significant cut-off for OM prediction in M1b patients. Moreover, internal validation with 2000 bootstrap resamples confirmed these findings. Finally, all results were virtually the same, when CSM represented the endpoint of interest.

Conclusions: We validated the OM reduction associated with EBRT in M1a and M1b patients with PSA ≤ 10.0 ng/ml but not in M1b patients with PSA > 10.0 ng/ml. In consequence, it appears that a smaller subset of North American mPCa patients benefit of EBRT than originally reported in European patients. Further North American validation studies are essential.
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http://dx.doi.org/10.1038/s41391-020-00276-2DOI Listing
March 2021

The Impact of Race and Age on Distribution of Metastases in Patients with Prostate Cancer.

J Urol 2020 Nov 12;204(5):962-968. Epub 2020 May 12.

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

Purpose: We investigated the effect of race and age on the distribution of prostate cancer metastases.

Materials And Methods: Records for patients with metastatic prostate cancer were abstracted from the National Inpatient Sample database (2008-2015).

Results: Of 6,963 patients with metastatic prostate cancer 3,881 (72.2%) were Caucasian and 1,494 (27.8%) were African American. Bone metastases were the most common site of metastases in Caucasian and African American patients (83.9% and 87.0%, respectively), followed by distant lymph node metastases in Caucasian (13.9% of Caucasian vs 13.2% of African American), liver metastases in African American (13.8% of African American vs 13.3% of Caucasian) and lung metastases in Caucasian and African American patients (9.3% and 13.1%, respectively). No clinically meaningful differences were recorded in age and race analyses, except for lymph node metastases (61.1% to 23.4% in Caucasian vs 39.0% to 25.1% in African American patients), which decreased with age. Specific single organ metastatic sites, outside of bone and lymph nodes, were low in both racial groups (2.1% or less). The rate of brain metastases was also rare in both racial groups at 1.4% or less, regardless of other metastatic locations. Thoracic metastases, in the absence of bone and abdominal metastases, were present in 1.9% of Caucasian and African American patients.

Conclusions: The most important finding according to age and race resided in rates of lymph node metastases. Conversely, all other racial and age related differences were subtle. Nonetheless, they are important in the context of planning and/or design of clinical trials. Finally, brain (1.4%) and thoracic (1.9%) metastases affect few patients and routine brain and chest imaging may not be warranted.
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http://dx.doi.org/10.1097/JU.0000000000001131DOI Listing
November 2020

[Salvage lymph node dissection for nodal recurrent prostate cancer].

Aktuelle Urol 2020 06 26;51(3):258-264. Epub 2020 Mar 26.

Universitätsklinikum Hamburg-Eppendorf, Martini-Klinik, Hamburg.

Recent advances in functional imaging, such as prostate-specific membrane antigen positron emission tomography (PSMA PET/CT), provide earlier detection of nodal recurrent prostate cancer. Current studies on metastasis-directed therapy in patients with node-only recurrence suggest a positive influence on the prognosis in selected patients. Nevertheless, most studies are retrospective and, due to a lack of high-level evidence, salvage lymph node dissection (SLND) is not recommended by current guidelines.The aim of this work is to provide a critical summary of the current data on SLND in patients with nodal recurrent prostate cancer with a focus on imaging procedures, extent of SLND and oncological outcome.European guidelines recommend the use of choline or PSMA PET/CT imaging if prostate cancer recurrence is suspected. PSMA PET/CT is superior to choline PET/CT in sensitivity and specificity and should be the preferred approach. Nevertheless, if SLND is performed, common practice is bilateral SLND - even if only unilateral lymph node involvement is detected by PSMA PET/CT. However, unilateral SLND can also be considered. A randomised prospective trial (ProSTone) is being initiated for clarification.PSMA radioguided surgery seems to be a new promising surgical approach. It facilitates the intraoperative detection of lymph node metastases. However, long-term data are still awaited.All in all, SLND achieves a respectable biochemical response rate in carefully selected patients. Nevertheless, prospective studies are necessary in the future in order to define the clinical usefulness more precisely.
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http://dx.doi.org/10.1055/a-1132-5180DOI Listing
June 2020

Preoperative frailty predicts adverse short-term postoperative outcomes in patients treated with radical prostatectomy.

Prostate Cancer Prostatic Dis 2020 12 18;23(4):573-580. Epub 2020 Mar 18.

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

Background: To investigate the effect of frailty on short-term postoperative outcomes in patients with prostate cancer treated with radical prostatectomy (RP).

Methods: Within the National Inpatient Sample database, we identified 91,618 RP patients treated between 2008 and 2015. The Johns Hopkins Adjusted Clinical Groups frailty-defining indicator was applied, and we examined the rates of frailty over time, as well as its effect on overall complications, major complications, nonhome-based discharge, length of stay (LOS), and total hospital charges (THCs). Time trends and multivariable logistic, Poisson and linear regression models were applied.

Results: Overall, 12,185 (13.3%) patients were frail. Rates of frail patients increased over time (from 10.3 to 18.2%; p < 0.001). Frail patients had higher rates of overall complications (16.6 vs. 8.6%), major complications (4.9 vs. 2.6%), nonhome-based discharge (5.9 vs. 5%), longer LOS (2 vs. 1), and higher THCs ($37,186 vs. $35,241) (all p < 0.001). Moreover, frailty was an independent predictor of overall complications (OR: 1.95), major complications (OR: 1.76), nonhome-based discharge (OR: 1.20), longer LOS (RR: 1.19), and higher THCs (RR: $3160) (all p < 0.001). Of frail patients, 10,418 (85.5%) neither exhibited body mass index ≥ 30 nor Charlson comorbidity index ≥ 2.

Conclusions: On average, every seventh RP patient is frail and that proportion is on the rise. Frail individuals are at higher risk of adverse short-term postoperative outcomes, that cannot be predicted by other risk factors, such as obesity or comorbidities.
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http://dx.doi.org/10.1038/s41391-020-0225-3DOI Listing
December 2020

Preoperative frailty predicts adverse short-term postoperative outcomes in patients treated with radical nephroureterectomy.

J Surg Oncol 2020 Mar 12;121(4):688-696. Epub 2020 Jan 12.

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

Background: To investigate the effect of frailty on short-term postoperative outcomes and total hospital charges (THCs) in patients with non-metastatic upper urinary tract carcinoma, treated with radical nephroureterectomy (RNU).

Methods: Within the National Inpatient Sample (NIS) database we identified 11 258 RNU patients (2000-2015). We used the Johns Hopkins frailty-indicator to stratify patients according to frailty status. Time trends and multivariable logistic, Poisson and linear regression models were applied.

Results: Overall, 1801 (16.0%) patients were frail, 4664 (41.4%) were older than 75 years and 1530 (13.6%) had Charlson comorbidity index ≥2. Rates of frail patients increased over time, from 7.3% to 24.9% (P < .001). Frail patients exhibited higher rates (all P < .05) of overall complications (62.6% vs 50.9%), in-hospital mortality (1.6% vs 1.0%), non-home-based discharge (22.7% vs 12.1%), longer length of stay (LOS) (6 vs 1 day) and higher THCs ($49 539 vs $39 644). Moreover, frailty independently predicted (all P < .05) overall complications (OR, 1.46), in-hospital mortality (OR, 1.52), non-home-based discharge (OR, 1.36), longer LOS (RR, 1.30) and higher THCs (RR, +$11 806).

Conclusion: Preoperative frailty is important in RNU patients. One of four RNU patients is frail. Moreover, frailty predicts short-term postoperative complications, as well as longer LOS and higher THCs after RNU.
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http://dx.doi.org/10.1002/jso.25840DOI Listing
March 2020