Publications by authors named "Fred Saad"

590 Publications

Tumor Stage and Substage Predict Cancer-specific Mortality After Nephrectomy for Nonmetastatic Renal Cancer: Histological Subtype-specific Validation.

Eur Urol Focus 2021 Feb 27. Epub 2021 Feb 27.

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

Background: For patients with nonmetastatic renal cell carcinoma (nmRCC) treated with nephrectomy, prediction of cancer-specific mortality (CSM) by T stage and substage has not been validated for the separate histological subtypes.

Objective: To investigate the ability of pathological T stage and substage to predict CSM for patients with clear-cell, papillary, or chromophobe nmRCC treated with nephrectomy.

Design, Setting, And Participants: Using the SEER database for 2004-2016, we identified 87 149 patients with T1-4 N0/X M0 nmRCC treated with nephrectomy for the clear-cell (65 715; 75.4%), papillary (14 587; 16.7%), or chromophobe (6847; 7.9%) histological subtype.

Outcome Measurements And Statistical Analysis: Kaplan-Meier plots and Cox regression models were used to estimate CSM.

Results And Limitations: For all three histological subtypes, patients with T1a-T3a disease exhibited more favorable CSM than patients with T3b-T4 RCC. For clear-cell RCC, there were clinically meaningful and statistically significant differences for virtually all intergroup comparisons among T1a-T3a stages. For papillary T1a-T3a RCC, clinically meaningful differences disappeared, although the statistical significance remained. For chromophobe T1a-T3a RCC, no clinically meaningful or statistically significant differences were observed. For all three histological subtypes, patients with T3b-T4 RCC exhibited virtually uniformly unfavorable CSM, with no clinically meaningful intergroup CSM differences.

Conclusion: The use of T stage and substage for stratification of patients with nmRCC treated with nephrectomy revealed differences in CSM among T1a-T3a cases, but not T3b-T4. The magnitude of the CSM difference was greatest for clear-cell, intermediate for papillary, and marginal for chromophobe RCC.

Patient Summary: For patients with kidney cancer, the stage of their disease assessed after surgery on the affected kidney can predict how likely they are to die from their cancer. This prediction varies for different subtypes of kidney cancer.
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http://dx.doi.org/10.1016/j.euf.2021.02.009DOI Listing
February 2021

Comparison between 1973 and 2004/2016 WHO grading systems in patients with Ta urothelial carcinoma of urinary bladder.

J Clin Pathol 2021 Feb 23. Epub 2021 Feb 23.

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

Aims: To compare the 1973 WHO and the 2004/2016 WHO grading systems in patients with urothelial carcinoma of urinary bladder (UCUB), since no consensus has been made which classification should supersede the other and since both are recommended in clinical practice.

Methods: Newly diagnosed patients with Ta UCUB treated with transurethral resection of bladder tumour were abstracted from the Surveillance, Epidemiology and End Results database (2010-2016). Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs G2 vs G3) and to 2004/2016 WHO (low-grade vs high-grade) grading systems.

Results: Of 35 986 patients, according to 1973 WHO grading system, 8165 (22.7%) were G1, 17 136 (47.6%) were G2 and 10 685 (29.7%) were G3. According to 2004/2016 WHO grading system, 24 961 (69.4%) were low-grade versus 11 025 (30.6%) high-grade. In multivariable CRMs, G3 (HR: 2.05, p<0.001), relative to G1, and high-grade(HR: 2.13, p<0.001), relative to low-grade, predicted higher CSM. Conversely, G2 (p=0.8) was not an independent predictor. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. After addition of 1973 WHO or 2004/2016 WHO grade, the accuracy increased to 76% and 77%, respectively.

Conclusions: From a statistical standpoint, it appears that the 2004/2016 WHO grading system holds a small, although measurable advantage over the 1973 WHO grading system. Other considerations, such as intraobserver and interobserver variability may represent an additional matric to consider in deciding which grading system is better.
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http://dx.doi.org/10.1136/jclinpath-2021-207400DOI Listing
February 2021

Race/Ethnicity Determines Life Expectancy in Surgically Treated T1aN0M0 Renal Cell Carcinoma Patients.

Eur Urol Focus 2021 Feb 17. Epub 2021 Feb 17.

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

Background: Life expectancy (LE) is an important consideration in the clinical decision-making for T1aN0M0 renal cell cancer (RCC) patients.

Objective: To test the effect of race/ethnicity (Caucasian, African American, Hispanic/Latino, and Asian) on LE predictions from Social Security Administration (SSA) life tables in male and female T1aN0M0 RCC patients.

Design, Setting, And Participants: We relied on the Surveillance, Epidemiology, and End Results database.

Intervention: Radical nephrectomy (RN) and partial nephrectomy (PN).

Outcome Measurements And Statistical Analysis: Five-year and 10-yr observed overall survival (OS) of pT1aN0M0 RCC patients treated between 2004 and 2006 were compared with the LE predicted from SSA life tables. We repeated the comparison in a more contemporary cohort (2009-2011), with 5-yr follow-up and higher PN rates.

Results And Limitations: In the 2004-2006 cohort, PN rate was 40.7%. OS followed the predicted LE in Caucasians, Hispanics/Latinos, and Asians, but not in African Americans, in whom 5-yr OS rates were 5.0% (male) and 8.7% (female) and 10-yr rates were 4.2% (male) and 11.1% (female) lower than predicted. In the 2009-2011 cohort, PN rate was 59.4%. Same observations were made for OS versus predicted LE in Caucasians, Hispanics/Latinos, and Asians. In African Americans, 5-yr OS rates were 1.5% (male) and 4.9% (female) lower than predicted.

Conclusions: In RN- or PN-treated pT1aN0M0 RCC patients, LE predictions closely approximated OS of Caucasians, Hispanics/Latinos, and Asians. In African-American patients, SSA life tables overestimated LE, more in females than in males. The limitations of our study are its retrospective nature, its validity for US patients only, and the under-representation of racial/ethnic minorities.

Patient Summary: Social Security Administration life tables can be used to estimate long-term life expectancy in patients who are surgically treated for renal cancer (≤4 cm). However, while for Caucasians, Hispanics/Latinos, and Asians, the prediction performs well, life expectancy of African Americans is generally overestimated by life table predictions. TAKE  HOME MESSAGE: In the clinical decision-making process for T1aN0M0 renal cell cancer patients eligible for radical or partial nephrectomy, the important influence of patient sex and race/ethnicity on life expectancy should be taken into account, when using Social Security Administration life tables.
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http://dx.doi.org/10.1016/j.euf.2021.02.004DOI 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 Feb 15. Epub 2021 Feb 15.

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
February 2021

Comparison Between Urothelial and Non-Urothelial Urethral Cancer.

Front Oncol 2020 29;10:629692. Epub 2021 Jan 29.

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

Background: To test the effect of variant histology relative to urothelial histology on stage at presentation, cancer specific mortality (CSM), and overall mortality (OM) after chemotherapy use, in urethral cancer.

Materials And Methods: Within the Surveillance, Epidemiology and End Results (2004-2016) database, we identified 1,907 primary variant histology urethral cancer patients. Kaplan-Meier plots, Cox regression analyses, cumulative incidence-plots, multivariable competing-risks regression models and propensity score matching for patient and tumor characteristics were used.

Results: Of 1,907 eligible urethral cancer patients, urothelial histology affected 1,009 (52.9%) vs. squamous cell carcinoma (SCC) 455 (23.6%) vs. adenocarcinoma 278 (14.6%) vs. other histology 165 (8.7%) patients. Urothelial histological patients exhibited lower stages at presentation than SCC, adenocarcinoma or other histology patients. In urothelial histology patients, five-year CSM was 23.5% vs. 34.4% in SCC [Hazard Ratio (HR) 1.57] vs. 40.7% in adenocarcinoma (HR 1.69) vs. 43.4% in other histology (HR 1.99, p < 0.001). After matching in multivariate competing-risks regression models, variant histology exhibited 1.35-fold higher CSM than urothelial. Finally, in metastatic urethral cancer, lower OM was recorded after chemotherapy in general, including metastatic adenocarcinoma and other variant histology subtypes, except metastatic SCC.

Conclusion: Adenocarcinoma, SCC and other histology subtypes affect fewer patients than urothelial histology. Presence of variant histology results in higher CSM. Finally, chemotherapy for metastatic urethral cancer improves survival in adenocarcinoma and other variant histology subtypes, but not in SCC.
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http://dx.doi.org/10.3389/fonc.2020.629692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880052PMC
January 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

Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors.

Prostate Cancer Prostatic Dis 2021 Feb 8. Epub 2021 Feb 8.

Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA.

Background: Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit-risk profile of potential treatments is required.

Methods: In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function.

Results And Conclusions: While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit-risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.
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http://dx.doi.org/10.1038/s41391-020-00310-3DOI Listing
February 2021

UPDATE - 2021 Canadian Urological Association (CUA)-Canadian Uro Oncology Group (CUOG) castration-resistant prostate cancer (CRPC) guideline: What has changed since 2019?

Authors:
Fred Saad

Can Urol Assoc J 2021 Feb;15(2):11-12

Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.

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http://dx.doi.org/10.5489/cuaj.7160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864712PMC
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

Sex-Related Differences Include Stage, Histology, and Survival in Urethral Cancer Patients.

Clin Genitourin Cancer 2021 Jan 6. Epub 2021 Jan 6.

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

Purpose: To test the effect of sex on histologic subtype, stage at presentation, treatment, and cancer-specific mortality (CSM) in urethral cancer.

Patients And Methods: We identified urethral cancer patients within the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2016). After matching for tumor and patient characteristics, cumulative incidence plots and multivariable competing risks regression models, adjusted for other-cause mortality, tested CSM according to sex.

Results: Of 1645 eligible urethral cancer patients, 1073 (65%) were male. Urothelial histologic subtype was most frequent in male (59%) but not female (27%) subjects. Adenocarcinoma, squamous cell carcinoma, and other histologies were more frequent in female patients. Most male subjects harbored T1N0M0 (32%) stage disease, whereas most female subjects harbored T3-4N0M0 (29%) stage disease. In urothelial and adenocarcinoma histologic subtypes, African American female subjects were most prevalent (31 and 78%) versus whites (16 and 52%) versus Hispanics (27 and 74%). In T1N0M0 stage, single-mode surgical treatment was more frequent in male than female patients (respectively, 73% vs 59%). In T3-4 and/or N1-2 stage disease, multimodal therapy was more frequent in female than male (42% vs 37%) patients. In nonmetastatic urethral cancer (T1-4N0-2M0), after propensity score matching for stage, race, treatment, and age, cumulative incidence plots showed 5-year CSM of 36% and 25% in female and male patients, respectively, and after further multivariable adjustment resulted in 1.3-fold higher CSM in female as opposed to male patients (P = .07).

Conclusion: Female patients with urethral cancer present with higher disease stage. Despite higher rates of multimodal therapy, and despite matching for stage disadvantage, female subjects with urethral cancer exhibited higher CSM.
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http://dx.doi.org/10.1016/j.clgc.2020.12.001DOI Listing
January 2021

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

THE CARDIOVASCULAR EFFECTS OF GNRH ANTAGONISTS IN MEN WITH PROSTATE CANCER.

Eur Heart J Cardiovasc Pharmacother 2021 Jan 20. Epub 2021 Jan 20.

Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, Canada.

Aims: The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists.

Methods And Results: We conducted a systematic review to identify all randomised, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified ten eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83) respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies.

Conclusions: There is consistent but methodologically limited data to suggest that GnRH antagonists - a relatively new class of androgen deprivation therapy for prostate cancer - cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.
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http://dx.doi.org/10.1093/ehjcvp/pvab005DOI Listing
January 2021

Comparing Perspectives of Canadian Men Diagnosed With Prostate Cancer and Health Care Professionals About Active Surveillance.

J Patient Exp 2020 Dec 11;7(6):1122-1129. Epub 2020 Jun 11.

Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal, Quebec, Canada.

Active surveillance (AS) has gained acceptance as a primary management approach for patients diagnosed with low-risk prostate cancer (PC). In this qualitative study, we compared perspectives between patients and health care professionals (HCP) to identify what may contribute to patient-provider discordance, influence patient decision-making, and interfere with the uptake of AS. We performed a systematic comparison of perspectives about AS reported from focus groups with men eligible for AS (7 groups, N = 52) and HCP (5 groups, N = 48) who engaged in conversations about AS with patient. We used conventional content analysis to scrutinize separately focus group transcripts and reached a consensus on similar or divergent viewpoints between them. Patients and clinicians agreed that AS was appropriate for low grade PC and understood the low-risk nature of the disease. They shared the perspective that disease status was a critical factor to pursue or discontinue AS. However, men expressed a greater emphasis on quality of life in their decisions related to AS. Patients and clinicians differed in their perspectives on the clarity, availability, and volume of information needed and offered; clinicians acknowledged variations between HCP when presenting AS, while patients were often compelled to seek additional information beyond what was provided by physicians and experienced difficulty in finding or interpreting information applicable to their situation. A greater understanding of discordant perspectives about AS between patients and HCP can help improve patient engagement and education, inform development of knowledge-based tools or aids for decision-making, and identify areas that require standardization across the clinical practice.
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http://dx.doi.org/10.1177/2374373520932735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786672PMC
December 2020

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

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

Urol Oncol 2021 Feb 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

Modulation of de Novo Lipogenesis Improves Response to Enzalutamide Treatment in Prostate Cancer.

Cancers (Basel) 2020 Nov 11;12(11). Epub 2020 Nov 11.

Institut du Cancer de Montréal, Montréal, QC H2X 0A9, Canada.

De novo lipogenesis (DNL) is now considered as a hallmark of cancer. The overexpression of key enzymes of DNL is characteristic of both primary and advanced disease and may play an important role in resistance to therapies. Here, we showed that DNL is highly enhanced in castrate resistant prostate cancer (CRPC) cells compared to hormone sensitive and enzalutamide resistant cells. This observation suggests that this pathway plays an important role in the initiation of aggressive prostate cancer and in the development of enzalutamide resistance. Importantly, here we show that both prostate cancer cells sensitive and resistant to enzalutamide are dependent on DNL to proliferate. We next combined enzalutamide with an inhibitor of Stearoyl CoA Desaturase 1 (SCD1), an important enzyme in DNL, and observed significantly reduced tumor growth caused by the important change in tumoral lipid desaturation. Our findings suggest that the equilibrium between monounsaturated fatty acids and saturated fatty acids is essential in the establishment of the more aggressive prostate cancer phenotype and that the combination therapy induces a disruption of this equilibrium leading to an important decrease of cell proliferation. These findings provide new insights into the role of DNL in the progression of prostate cancer cells. The study also provides the rationale for the use of an inhibitor of SCD1 in combination with enzalutamide to improve response, delay enzalutamide resistance and improve disease free progression.
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http://dx.doi.org/10.3390/cancers12113339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698241PMC
November 2020

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

PUMA and NOXA Expression in Tumor-Associated Benign Prostatic Epithelial Cells Are Predictive of Prostate Cancer Biochemical Recurrence.

Cancers (Basel) 2020 Oct 29;12(11). Epub 2020 Oct 29.

Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM) et Institut du Cancer de Montréal (ICM), Montreal, QC H2X 0A9, Canada.

Background: Given that treatment decisions in prostate cancer (PC) are often based on risk, there remains a need to find clinically relevant prognostic biomarkers to stratify PC patients. We evaluated PUMA and NOXA expression in benign and tumor regions of the prostate using immunofluorescence techniques and determined their prognostic significance in PC.

Methods: PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples ( = 285). TMAs were constructed using two cores of benign tissue and two cores of tumor tissue from each patient. Association between biomarker expression and biochemical recurrence (BCR) at 3 years was established using log-rank (LR) and multivariate Cox regression analyses.

Results: Kaplan-Meier analysis showed a significant association between BCR and extreme levels (low or high) of PUMA expression in benign epithelial cells (LR = 8.831, = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, < 0.001) in Kaplan-Meier and in a multivariate Cox regression analyses (HR: 2.935 (1.645-5.236), < 0.001).

Conclusions: The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.
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http://dx.doi.org/10.3390/cancers12113187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692508PMC
October 2020

Newly Diagnosed High-Risk Prostate Cancer in an Era of Rapidly Evolving New Imaging: How Do We Treat?

J Clin Oncol 2021 Jan 13;39(1):13-16. Epub 2020 Oct 13.

Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.

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http://dx.doi.org/10.1200/JCO.20.02268DOI Listing
January 2021

Can Exercise Adaptations Be Maintained in Men with Prostate Cancer Following Supervised Programmes? Implications to the COVID-19 Landscape of Urology and Clinical Exercise.

Eur Urol Open Sci 2020 Oct 2;21:47-50. Epub 2020 Oct 2.

Exercise Medicine Research Institute, Edith Cowan University, Perth, Western Australia, Australia.

In this brief correspondence, we evaluate the potential impact of pivoting from face-to-face supervised to unsupervised home-based exercise programmes to contextualise the coronavirus disease 2019 (COVID-19) pandemic in prostate cancer patients. A meta-analysis was undertaken in fatigue, quality of life, and lean and fat mass outcomes in the four studies included. Our analysis indicates that unsupervised home-based exercise maintains patient-reported outcomes, except for fat mass. In summary, changing to unsupervised exercise is unlikely to provide further benefits on patient-reported and body composition outcomes, but may help maintain initial gains during physical distancing restrictions.

Patient Summary: We discuss the potential impacts of transitioning from face-to-face supervised to unsupervised home-based exercise programmes in prostate cancer patients during the coronavirus disease 2019 (COVID-19) pandemic. Our analysis suggests that patients are likely to maintain patient-reported and body composition benefits from current nonsupervised programmes; however, evolution of exercise delivery to prostate cancer patients is required to continue health and fitness improvement in this group.
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http://dx.doi.org/10.1016/j.euros.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531928PMC
October 2020

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

Urol Oncol 2020 Oct 6. 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
October 2020