Publications by authors named "Zhe Tian"

362 Publications

Immuno-oncology therapy in metastatic bladder cancer: a systematic review and network meta-analysis.

Crit Rev Oncol Hematol 2021 Nov 22:103534. Epub 2021 Nov 22.

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

Context: Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void.

Objective: To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1 and 2 line IO-based regimens.

Materials And Methods: PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs.

Results: Overall, 3,255 and 1,452 patients were respectively included in the first- and second-line settings. In 1 line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2 line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2 line CT.

Conclusions: In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1 line setting. However, pembrolizumab holds a survival benefit in 2 line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103534DOI Listing
November 2021

Treatment of Ureteral Stent-Related Symptoms.

Urol Int 2021 Nov 2:1-16. Epub 2021 Nov 2.

Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, University of Turin, Turin, Italy.

Background: The aim of the study was to assess the effectiveness of the main classes of drugs used at reducing morbidity related to ureteric stents.

Summary: After establishing a priori protocol, a systematic electronic literature search was conducted in July 2019. The randomized clinical trials (RCTs) selection proceeded in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered (PROSPERO ID 178130). The risk of bias and the quality assessment of the included RCTs were performed. Ureteral Stent Symptom Questionnaire (USSQ), International Prostate Symptom Score (IPSS), and quality of life (QoL) were pooled for meta-analysis. Mean difference and risk difference were calculated as appropriate for each outcome to determine the cumulative effect size. Fourteen RCTs were included in the analysis accounting for 2,842 patients. Alpha antagonist, antimuscarinic, and phosphodiesterase (PDE) inhibitors significatively reduced all indexes of the USSQ, the IPSS and QoL scores relative to placebo. Conversely, combination therapy (alpha antagonist plus antimuscarinic) showed in all indexes of the USSQ, IPSS, and QoL over alpha antagonist or antimuscarinic alone. On comparison with alpha blockers, PDE inhibitors were found to be equally effective for urinary symptoms, general health, and body pain parameters, but sexual health parameters improved significantly with PDE inhibitors. Finally, antimuscarinic resulted in higher decrease in all indexes of the USSQ, the IPSS, and QoL relative to alpha antagonist. Key message: Relative to placebo, alpha antagonist alone, antimuscarinics alone, and PDE inhibitors alone have beneficial effect in reducing stent-related symptoms. Furthermore, there are significant advantages of combination therapy compared with monotherapy. Finally, PDE inhibitors are comparable to alpha antagonist, and antimuscarinic seems to be more effective than alpha antagonist alone.
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http://dx.doi.org/10.1159/000518387DOI Listing
November 2021

Survival after radical prostatectomy vs. radiation therapy in ductal carcinoma of the prostate.

Int Urol Nephrol 2021 Nov 19. Epub 2021 Nov 19.

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

Aim: To compare cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs. external beam radiotherapy (RT) in patients with ductal carcinoma (DC) of the prostate.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified 369 DC patients, of whom 303 (82%) vs. 66 (18%) were treated with RP vs. RT, respectively. Kaplan-Meier plots and uni- and stepwise multivariate Cox regression models addressed CSM in the unmatched population. After propensity score matching (PSM) and inverse probability of treatment weighting (IPTW), Kaplan-Meier curve and Cox regression models tested the effect of RP vs RT on CSM.

Results: Overall, RT patients were older, harbored higher PSA values, higher clinical T and higher Gleason grade groups. 5-year CSM rates were respectively 4.2 vs. 10% for RP vs. RT (HR 0.40, 95% CI 0.16-0.99, p = 0.048, favoring RP). At step-by-step multivariate Cox regression, after adding possible confounders, the central tendency of the HR for RP vs. RT approached 1. PSM resulted into 124 vs. 53 patients treated respectively with RP vs. RT. After PSM, as well as after IPTW, the protective effect of RP was no longer present (HR 1.16, 95% CI 0.23-5.73, p = 0.9 and 0.97, 95% CI 0.35-2.66, p = 0.9, respectively).

Conclusions: Although CSM rate of ductal carcinoma RP patients is lower of that of RT patients, this apparent benefit disappears after statistical adjustment for population differences.
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http://dx.doi.org/10.1007/s11255-021-03070-8DOI Listing
November 2021

Cancer-specific mortality after radical prostatectomy vs external beam radiotherapy in high-risk Hispanic/Latino prostate cancer patients.

Int Urol Nephrol 2021 Nov 16. Epub 2021 Nov 16.

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

Purpose: To test for differences in cancer-specific mortality (CSM) rates in Hispanic/Latino prostate cancer patients according to treatment type, radical prostatectomy (RP) vs external beam radiotherapy (EBRT).

Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 2290 NCCN (National Comprehensive Cancer Network) high-risk (HR) Hispanic/Latino prostate cancer patients. Of those, 893 (39.0%) were treated with RP vs 1397 (61.0%) with EBRT. First, cumulative incidence plots and competing risks regression models tested for CSM differences after adjustment for other cause mortality (OCM). Second, cumulative incidence plots and competing risks regression models were refitted after 1:1 propensity score matching (according to age, PSA, biopsy Gleason score, cT-stage, cN-stage).

Results: In NCCN HR patients, 5-year CSM rates for RP vs EBRT were 2.4 vs 4.7%, yielding a multivariable hazard ratio of 0.37 (95% CI 0.19-0.73, p = 0.004) favoring RP. However, after propensity score matching, the hazard ratio of 0.54 was no longer statistically significant (95% CI 0.21-1.39, p = 0.2).

Conclusion: Without the use of strictest adjustment for population differences, NCCN high-risk Hispanic/Latino prostate cancer patients appear to benefit more of RP than EBRT. However, after strictest adjustment for baseline patient and tumor characteristics between RP and EBRT cohorts, the apparent CSM benefit of RP is no longer statistically significant. In consequence, in Hispanic/Latino NCCN high-risk patients, either treatment modality results in similar CSM outcome.
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http://dx.doi.org/10.1007/s11255-021-03055-7DOI Listing
November 2021

Removal of denatured protein particles enhanced UASB treatment of oxytetracycline production wastewater.

Sci Total Environ 2021 Nov 10:151549. Epub 2021 Nov 10.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Science, Post Office Box 2871, Beijing 100085, China; National Engineering Research Center of Industrial Wastewater Detoxication and Resource Recovery, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Enhanced hydrolysis, which can selectively destroy antibiotic potency, has been previously demonstrated to be an effective pretreatment technology for the biological treatment of antibiotic production wastewater. However, full-scale application of enhanced hydrolysis to the treatment of real oxytetracycline production wastewater showed that the up-flow anaerobic sludge blanket (UASB) reactors treating the pretreated wastewater could only be stable under a low organic loading rate (OLR) of 1.8 ± 0.4 g·COD/L/d. Deterioration of UASB was also confirmed in treating the same wastewater using a bench-scale reactor (R1) at an OLR of 4.4 ± 0.3 g·COD/L/d. Assuming that the particles formed due to the denaturation of soluble proteins under the hydrolysis temperature (110 °C), resulting in the significant increase of suspended solids (SS) in oxytetracycline production wastewater from less than 200 mg/L to 1200 ± 500 mg/L, were responsible for the deterioration of UASB, the pretreated wastewater was filtered using polypropylene cotton fiber and ultrafiltration membrane, and then fed into two parallel bench-scale UASB reactors (R2 and R3). Both reactors maintained a stable COD removal (53.2% ~ 61.1%) even at an OLR as high as 8.0 g·COD/L/d. When the feed of R3 was switched to unfiltered wastewater, however, deterioration of the reactor occurred again. Microscopic observation showed that the granules in R3 were fully covered by protein particles after the switch of the feed. It was possible that the tight layer of the denatured protein particles blocked the inner pores of the granules, resulting in the obstruction of substrate transfer and biogas emission, while removing the protein particles could abate such blockage problem. This study provides a scientific basis for the efficient treatment of antibiotic production wastewater.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151549DOI Listing
November 2021

The Effect of 10 Most Common Nonurological Primary Cancers on Survival in Men With Secondary Prostate Cancer.

Front Oncol 2021 6;11:754996. Epub 2021 Oct 6.

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

Background: This study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa).

Material And Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer secondary PCa diagnoses.

Results: We identified 24,848 secondary PCa patients (skin,  = 3,871; rectal,  = 798; colon,  = 3,665; lymphoma,  = 2,583; leukemia,  = 1,102; pancreatic,  = 118; stomach,  = 361; esophagus,  = 219; liver,  = 160; lung,  = 1,328) 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa.

Conclusion: Patients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.
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http://dx.doi.org/10.3389/fonc.2021.754996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526938PMC
October 2021

Cancer-specific survival after radical prostatectomy versus external beam radiotherapy in high-risk and very high-risk African American prostate cancer patients.

Prostate 2021 Oct 18. Epub 2021 Oct 18.

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

Background: To test for differences in cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network (NCCN) high-risk African American patients, as well as Johns Hopkins University (JHU) high-risk and very high-risk patients.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 4165 NCCN high-risk patients, of whom 1944 (46.7%) and 2221 (53.3%) patients qualified for JHU high-risk or very high-risk definitions. Of all 4165 patients, 1390 (33.5%) were treated with RP versus 2775 (66.6%) with EBRT. Cumulative incidence plots and competing risks regression models addressed CSM before and after 1:1 propensity score matching between RP and EBRT NCCN high-risk patients. Subsequently, analyses were repeated separately in JHU high-risk and very high-risk subgroups. Finally, all analyses were repeated after landmark analyses were applied.

Results: In the NCCN high-risk cohort, 5-year CSM rates for RP versus EBRT were 2.4 versus 5.2%, yielding a multivariable hazard ratio of 0.50 (95% confidence interval [CI] 0.30-0.84, p = 0.009) favoring RP. In JHU very high-risk patients 5-year CSM rates for RP versus EBRT were 3.7 versus 8.4%, respectively, yielding a multivariable hazard ratio of 0.51 (95% CI: 0.28-0.95, p = 0.03) favoring RP. Conversely, in JHU high-risk patients, no significant CSM difference was recorded between RP vs EBRT (5-year CSM rates: 1.3 vs 1.3%; multivariable hazard ratio: 0.55, 95% CI: 0.16-1.90, p = 0.3). Observations were confirmed in propensity score-matched and landmark analyses adjusted cohorts.

Conclusions: In JHU very high-risk African American patients, RP may hold a CSM advantage over EBRT, but not in JHU high-risk African American patients.
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http://dx.doi.org/10.1002/pros.24253DOI Listing
October 2021

Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.

Prostate 2021 Oct 11. Epub 2021 Oct 11.

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

Background: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy.

Methods: We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM).

Results: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages.

Conclusions: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.
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http://dx.doi.org/10.1002/pros.24249DOI Listing
October 2021

Radical Cystectomy vs. Radiotherapy in Urothelial Bladder Cancer in Elderly and Very Elderly Patients.

Clin Genitourin Cancer 2021 Sep 1. Epub 2021 Sep 1.

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

Introduction: Controversy regarding cancer-specific mortality (CSM) of elderly and very elderly patients with muscle-invasive, non-metastatic, urothelial carcinoma of the urinary bladder (UCUB) undergoing radical cystectomy (RC) vs radiotherapy (RT) still exists.

Materials And Methods: In the 2004-2016 Surveillance, Epidemiology and End Results (SEER) database, we identified 2663 UCUB patients aged 75-79 (1808 RC vs 855 RT) and 3569 UCUB patients aged 80-89 (1551 RC vs 2018 RT). After stratification for concomitant chemotherapy, propensity score matching (PSM) between RC and RT was applied and competing-risks regression models addressed CSM and OCM.

Results: In the cohort aged 75-79, five-year CSM rates were 22.0 vs 49.0% for RC only vs RT only and yielded a HR of 0.41 (95% confidence interval (CI) 0.30-0.57, p<0.001) favoring RC only. Five-year CSM rates were 28.3 vs 44.3% for RC with chemotherapy vs trimodal therapy (TMT) and yielded a HR of 0.48 (95% CI 0.35-0.65, p<0.001) favoring RC with chemotherapy. In the cohort aged 80-89, five-year CSM rates were 24.2 vs 48.9% for RC only vs RT only and yielded a HR of 0.42 (95% CI 0.33-0.52, p<0.001) favoring RC only. Five-year CSM rates were 19.6 vs 43.2% for RC with chemotherapy vs TMT and yielded a HR of 0.43 (95% CI 0.28-0.67, p<0.001) favoring RC with chemotherapy.

Conclusions: In elderly and very elderly patients, radical cystectomy is associated with virtually half the CSM rate than radiotherapy, regardless of concomitant chemotherapy administration.
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http://dx.doi.org/10.1016/j.clgc.2021.08.003DOI Listing
September 2021

Survival after Radical Prostatectomy versus Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer.

J Urol 2021 Sep 24:101097JU0000000000002250. Epub 2021 Sep 24.

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

Purpose: Our goal was to compare cancer specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network© (NCCN©) high risk (HR) patients, as well as in Johns Hopkins University (JH) HR and very high risk (VHR) subgroups.

Materials And Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2016), we identified 24,407 NCCN HR patients, of whom 10,300 (42%) vs 14,107 (58%) patients that qualified for JH HR vs VHR, respectively. Overall, 9,823 (40%) underwent RP vs 14,584 (60%) EBRT. Cumulative incidence plots and competing-risks regression addressed CSM after 1:1 propensity score matching (according to age, prostate specific antigen, clinical T and N stages, and biopsy Gleason score) between RP and EBRT patients. All analyses addressed the combined NCCN HR cohort, as well as in JH HR and JH VHR subgroups.

Results: In the combined NCCN HR cohort 5-year CSM rates were 2.3% for RP vs 4.1% for EBRT and yielded a multivariate hazard ratio of 0.68 (95% CI 0.54-0.86, p <0.001) favoring RP. In VHR patients 5-year CSM rates were 3.5% for RP vs 6.0% for EBRT, yielding a multivariate hazard ratio of 0.58 (95% CI 0.44-0.77, p <0.001) favoring RP. Conversely, in HR patients no significant difference was recorded between RP vs EBRT (HR 0.7, 95% CI 0.39-1.25, p=0.2).

Conclusions: Our data suggest that RP holds a CSM advantage over EBRT in the combined NCCN HR cohort, and in its subgroup of JH VHR patients.
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http://dx.doi.org/10.1097/JU.0000000000002250DOI Listing
September 2021

External beam radiotherapy and radical prostatectomy are associated with better survival in Asian prostate cancer patients.

Int J Urol 2021 Sep 22. Epub 2021 Sep 22.

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

Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients.

Methods: In the Surveillance, Epidemiology and End Results database 2004-2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics.

Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2).

Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.
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http://dx.doi.org/10.1111/iju.14701DOI Listing
September 2021

Clinical Outcomes and Adverse Events after First-Line Treatment in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis.

J Urol 2021 Sep 21:101097JU0000000000002252. Epub 2021 Sep 21.

Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada.

Purpose: Four recent first-line clinical trials leveraging immune-oncology agents demonstrated an overall survival (OS) benefit relative to sunitinib. We aimed to provide formal comparisons among immune-oncology combinations in terms of OS, progression-free survival (PFS), objective response rates (ORR) and treatment-related adverse events (AEs).

Materials And Methods: PubMed® database was searched for studies indexed from January 1, 2016 through March 6, 2021. Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included: CheckMate 214 (nivolumab plus ipilimumab [N+I]), KEYNOTE-426 (pembrolizumab plus axitinib [P+A]), CheckMate 9ER (nivolumab plus cabozantinib [N+C]) and KEYNOTE-581 (lenvatinib plus permbrolizumab [L+P]). OS represented the primary outcome. PFS, ORR and AEs represented secondary outcomes.

Results: Overall, 3,320 patients were included. Regarding OS, N+C ranked first, followed by L+P, P+A and N+I. Regarding PFS and ORR, L+P ranked first, followed by N+C, P+A and N+I. Finally, N+I ranked first with respect to lowest grade 3+ AEs, followed by P+A, N+C and L+P. Differences in followup duration, risk grouping and nephrectomy rates distinguish the studies.

Conclusions: N+C may provide the most favorable OS, L+P the most favorable PFS and ORRs, and N+I the lowest toxicity. Population differences may potentially undermine the generalizability and the robustness of findings of metastatic renal cell carcinoma.
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http://dx.doi.org/10.1097/JU.0000000000002252DOI Listing
September 2021

Improvement in overall and cancer-specific survival in contemporary, metastatic prostate cancer chemotherapy exposed patients.

Prostate 2021 Dec 15;81(16):1374-1381. Epub 2021 Sep 15.

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

Introduction: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void.

Materials And Methods: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided between historical (2004-2013) versus contemporary (2014-2016). Chemotherapy rates were plotted over time. Kaplan-Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses.

Results: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001).

Conclusions: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.
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http://dx.doi.org/10.1002/pros.24235DOI Listing
December 2021

Increased risk of postoperative in-hospital complications after radical prostatectomy in patients with prior organ transplant.

Prostate 2021 Dec 13;81(16):1294-1302. Epub 2021 Sep 13.

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

Background: To analyze postoperative, in-hospital, complication rates in patients with organ transplantation before radical prostatectomy (RP).

Methods: From National Inpatient Sample (NIS) database (2000-2015) prostate cancer patients treated with RP were abstracted and stratified according to prior organ transplant versus nontransplant. Multivariable logistic regression models predicted in-hospital complications.

Results: Of all eligible 202,419 RP patients, 216 (0.1%) underwent RP after prior organ transplantation. Transplant RP patients exhibited higher proportions of Charlson comorbidity index ≥2 (13.0% vs. 3.0%), obesity (9.3% vs. 5.6%, both p < 0.05), versus to nontransplant RP. Of transplant RP patients, 96 underwent kidney (44.4%), 44 heart (20.4%), 40 liver (18.5%), 30 (13.9%) bone marrow, <11 lung (<5%), and <11 pancreatic (<5%) transplantation before RP. Within transplant RP patients, rates of lymph node dissection ranged from 37.5% (kidney transplant) to 60.0% (bone marrow transplant, p < 0.01) versus 51% in nontransplant patients. Regarding in-hospital complications, transplant patients more frequently exhibited, diabetic (31.5% vs. 11.6%, p < 0.001), major (7.9% vs. 2.9%) cardiac complications (3.2% vs. 1.2%, p = 0.01), and acute kidney failure (5.1% vs. 0.9%, p < 0.001), versus nontransplant RP. In multivariable logistic regression models, transplant RP patients were at higher risk of acute kidney failure (odds ratio [OR]: 4.83), diabetic (OR: 2.81), major (OR: 2.39), intraoperative (OR: 2.38), cardiac (OR: 2.16), transfusion (OR: 1.37), and overall complications (1.36, all p < 0.001). No in-hospital mortalities were recorded in transplant patients after RP.

Conclusions: Of all transplants before RP, kidney ranks first. RP patients with prior transplantation have an increased risk of in-hospital complications. The highest risk, relative to nontransplant RP patients appears to acute kidney failure.
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http://dx.doi.org/10.1002/pros.24224DOI Listing
December 2021

Stage and cancer-specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population-based study.

Int J Urol 2021 Dec 3;28(12):1247-1252. Epub 2021 Sep 3.

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

Objectives: To examine the effect of specific Asian ethnic subgroups on stage at presentation and cancer-specific mortality in non-metastatic upper tract urothelial carcinoma among North American upper tract urothelial carcinoma Asian patients treated with radical nephroureterectomy.

Methods: We relied on the Surveillance, Epidemiology and End Results database, from 2004 to 2016. Kaplan-Meier plots and multivariable Cox regression models predicting cancer-specific mortality were used.

Results: Of 584 upper tract urothelial carcinoma patients, 173 (29.6%) were Chinese versus 130 (22.3%) Japanese versus 68 (11.6%) Korean versus 64 (11.0%) Filipino versus 40 (6.8%) Vietnamese versus 109 (18.7%) other. Vietnamese and Chinese patients showed the highest rates of T N M and/or T N M (25.0% and 18.5%, respectively), relative to other Asian ethnic subgroups. In Kaplan-Meier plots, Vietnamese patients showed the highest cancer-specific mortality rate. In multivariable models, Vietnamese ethnicity also independently predicted higher cancer-specific mortality (hazard ratio 2.15, P = 0.02 and hazard ratio 1.96, P = 0.03), relative to Japanese and Chinese patients. All other Asian ethnic subgroups showed similar cancer-specific mortality patterns.

Conclusion: Vietnamese and Chinese patients are at a stage disadvantage at upper tract urothelial carcinoma diagnosis, relative to all other Asian ethnicities. After adjustment for stage, only Vietnamese patients showed a survival disadvantage relative to all other Asian ethnic subgroups. As a result, it appears that Vietnamese patients not only present at a higher upper tract urothelial carcinoma stage, but additionally appear to harbor upper tract urothelial carcinoma that progresses at a faster rate than in other Asian ethnic subgroups.
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http://dx.doi.org/10.1111/iju.14682DOI Listing
December 2021

Temporal trends, tumor characteristics and stage-specific survival in penile non-squamous cell carcinoma vs. squamous cell carcinoma.

Cancer Causes Control 2021 Sep 2. Epub 2021 Sep 2.

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

Purpose: To compare Cancer-specific mortality (CSM) in patients with Squamous cell carcinoma (SCC) vs. non-SCC penile cancer, since survival outcomes may differ between histological subtypes.

Methods: Within the Surveillance, Epidemiology and End Results database (2004-2016), penile cancer patients of all stages were identified. Temporal trend analyses, cumulative incidence and Kaplan-Meier plots, multivariable Cox regression and Fine and Gray competing-risks regression analyses tested for CSM differences between non-SCC vs. SCC penile cancer patients.

Results: Of 4,120 eligible penile cancer patients, 123 (3%) harbored non-SCC vs. 4,027 (97%) SCC. Of all non-SCC patients, 51 (41%) harbored melanomas, 42 (34%) basal cell carcinomas, 10 (8%) adenocarcinomas, eight (6.5%) skin appendage malignancies, six (5%) epithelial cell neoplasms, two (1.5%) neuroendocrine tumors, two (1.5%) lymphomas, two (1.5%) sarcomas. Stage at presentation differed between non-SCC vs. SCC. In temporal trend analyses, non-SCC diagnoses neither decreased nor increased over time (p > 0.05). After stratification according to localized, locally advanced, and metastatic stage, no CSM differences were observed between non-SCC vs. SCC, with 5-year survival rates of 11 vs 11% (p = 0.9) for localized, 33 vs. 37% (p = 0.4) for locally advanced, and 1-year survival rates of 37 vs. 53% (p = 0.9) for metastatic penile cancer, respectively. After propensity score matching for patient and tumor characteristics and additional multivariable adjustment, no CSM differences between non-SCC vs. SCC were observed.

Conclusion: Non-SCC penile cancer is rare. Although exceptions exist, on average, non-SCC penile cancer has comparable CSM as SCC penile cancer patients, after stratification for localized, locally invasive, and metastatic disease.
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http://dx.doi.org/10.1007/s10552-021-01493-3DOI Listing
September 2021

The impact of race/ethnicity on upstaging and/or upgrading rates among intermediate risk prostate cancer patients treated with radical prostatectomy.

World J Urol 2021 Aug 26. Epub 2021 Aug 26.

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

Background: Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a subgroup of IR PCa patients treated with radical prostatectomy (RP).

Methods: We relied on the Surveillance, Epidemiology and End Results 2004-2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting upstaging (pT3+/pN1) and/or upgrading (Gleason Grade Group [GGG] 4-5) at RP.

Results: Of 20,391 IR PCa patients, 15,050 (73.8%) were Caucasian, 2857 (14.0%) African-American, 1632 (8.0%) Hispanic/Latino and 852 (4.2%) Asian. Asian patients exhibited highest age (64 year), highest PSA (6.8 ng/ml) and highest rate of GGG3 (31.9%). African-Americans exhibited the highest percentage of positive cores at biopsy (41.7%) and the highest proportion of NCCN unfavorable risk group membership (54.6%). Conversely, Caucasians exhibited the highest proportion of cT2 stage (35.6%). In univariable analyses, Hispanic/Latinos exhibited the highest rates of upstaging/upgrading among all race/ethnicities, in both favorable and unfavorable groups, followed by Asians, Caucasians and African-Americans in that order. In multivariable analyses, Hispanic/Latino race/ethnicity represented an independent predictor of higher upstaging and/or upgrading in favorable IR PCa (odds ratio [OR] 1.27, p < 0.01), while African-American race/ethnicity represented an independent predictor of lower upstaging and/or upgrading in unfavorable IR PCa (OR 0.79, p < 0.001).

Conclusion: Race/ethnicity predisposes to differences in clinical, as well as in pathological characteristics in IR PCa patients. Specifically, even after full statistical adjustment, Hispanic/Latinos are at higher and African-Americans are at lower risk of upstaging and/or upgrading.
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http://dx.doi.org/10.1007/s00345-021-03816-0DOI Listing
August 2021

Clinical impact of whole-body 68Ga-PSMA I&T PET/CT: lesion frequency and added benefit in lower extremities.

Nuklearmedizin 2021 Dec 20;60(6):417-424. Epub 2021 Aug 20.

Department for Diagnostic and Interventional Radiology and Nuclear Medicine, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Aim: Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography (Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted.

Methods: We retrospectively analyzed 1,068 PCa patients who received Ga-PSMA I&T PET/CT in a single institution (2016-2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients.

Results: Of 1,068 Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy.

Conclusion: Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols.
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http://dx.doi.org/10.1055/a-1542-6064DOI Listing
December 2021

The effect of primary urological cancers on survival in men with secondary prostate cancer.

Prostate 2021 Nov 16;81(15):1149-1158. Epub 2021 Aug 16.

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

Background: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa).

Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses.

Results: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis.

Conclusions: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.
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http://dx.doi.org/10.1002/pros.24209DOI Listing
November 2021

Median time to progression with TKI-based therapy after failure of immuno-oncology therapy in metastatic kidney cancer: A systematic review and meta-analysis.

Eur J Cancer 2021 09 12;155:245-255. Epub 2021 Aug 12.

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

Background: The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy estimates have never been generated in these reports. We addressed this void.

Material And Methods: We systematically examined TKI efficacy after IO-failure and generated weighted median progression-free survival (PFS) estimates for Pazopanib, Axitinib, Cabozantinib, Sunitinib. A systematic review according to PRISMA was conducted. PubMed and abstracts were queried. Only studies proving median PFS were included. Weighted medians were computed for each TKI alternative.

Results: Of 245 articles, nine eligible studies were included in the current study with 952 analysed patients. Weighted PFS medians after any previous IO-based therapy were respectively 13.7 (range from 4.6 to 24.4), 8.1 (range from 4.7 to 13.2), 8.5 (range from 4.7 to 15.2) and 6.9 months (range from 2.9 to 11.6) for Pazopanib, Axitinib, Cabozantinib, Sunitinib. Specific second-line weighted PFS median was 14.8 months (range from 5.6 to 24.4), 10.1 months (range from 6.4 to 13.2), 8.7 months (range from 4.7 to 15.2) and 6.0 months (range from 2.9 to 8.0) for Pazopanib, Axitinib, Cabozantinib, Sunitinib, respectively, after first-line IO.

Conclusion: Pazopanib results in the longest weighted median PFS, after previous IO-failure, regardless of treatment line, as well as in specific second-line, post-first-line IO failure settings. Pending novel studies, Pazopanib appears to represent the most promising treatment option after prior IO.
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http://dx.doi.org/10.1016/j.ejca.2021.07.014DOI Listing
September 2021

Regional differences in patient age and prostate cancer characteristics and rates of treatment modalities in favorable and unfavorable intermediate risk prostate cancer across United States SEER registries.

Cancer Epidemiol 2021 10 5;74:101994. Epub 2021 Aug 5.

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

Background: Intermediate risk (IR) prostate cancer (PCa) is a highly heterogeneous entity and can be distinguished into favorable and unfavorable IR PCa according to biopsy, PSA and cT-stage characteristics. These differences may translate into differences in treatment type.

Methods: We tested for differences in PCa tumor characteristics and differences in active treatment rates (radical prostatectomy [RP], external beam radiotherapy [EBRT]) according to Surveillance, Epidemiology and End Results (SEER) registry (2010-2015) in favorable and unfavorable IR PCa. Data were stratified according to individual SEER registries. Further analyses additionally adjusted for PCa baseline characteristics (PSA, cT stage, biopsy Gleason group grading [GGG], percentage of positive biopsy cores).

Results: Tabulations according to SEER registries showed that, in favorable IR vs. unfavorable IR, the rates of RP and EBRT respectively ranged from 30.0 to 54.3% vs. 30.3-55.5 % and 8.3-44.7 % vs. 11.5-45.5 %. Differences in age and baseline PCa tumor characteristics also existed in both favorable and unfavorable IR across SEER registries. After adjustment for those baseline patient and PCa characteristics (PSA, cT stage, GGG, percentage of positive biopsy cores), RP and EBRT rates exhibited virtually no residual differences across individual SEER registries, in both favorable (36.0-41.0 % and 26.8-28.1 %) and unfavorable IR PCa (39.2-42.0% and 31.1-33.5 %).

Conclusion: Important differences may be identified in treatment rates within the examined 18 SEER registries in favorable and in unfavorable IR PCa. However, the observed differences are virtually entirely explained by differences in baseline PCa characteristics.
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http://dx.doi.org/10.1016/j.canep.2021.101994DOI Listing
October 2021

Nomogram Predicting Downgrading in National Comprehensive Cancer Network High-risk Prostate Cancer Patients Treated with Radical Prostatectomy.

Eur Urol Focus 2021 Jul 29. Epub 2021 Jul 29.

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

Background: Some high-risk prostate cancer (PCa) patients may show more favorable Gleason pattern at radical prostatectomy (RP) than at biopsy.

Objective: To test whether downgrading could be predicted accurately.

Design, Setting, And Participants: Within the Surveillance, Epidemiology and End Results database (2010-2016), 6690 National Comprehensive Cancer Network (NCCN) high-risk PCa patients were identified.

Outcome Measurements And Statistical Analyses: We randomly split the overall cohort between development and validation cohorts (both n = 3345, 50%). Multivariable logistic regression models used biopsy Gleason, prostate-specific antigen, number of positive prostate biopsy cores, and cT stage to predict downgrading. Accuracy, calibration, and decision curve analysis (DCA) tested the model in the external validation cohort.

Results And Limitations: Of 6690 patients, 50.3% were downgraded at RP, and of 2315 patients with any biopsy pattern 5, 44.1% were downgraded to RP Gleason pattern ≤4 + 4. Downgrading rates were highest in biopsy Gleason pattern 5 + 5 (84.1%) and lowest in 3 + 4 (4.0%). In the validation cohort, the logistic regression model-derived nomogram predicted downgrading with 71.0% accuracy, with marginal departures (±3.3%) from ideal predictions in calibration. In DCA, a net benefit throughout all threshold probabilities was recorded, relative to treat-all or treat-none strategies and an algorithm based on an average downgrading rate of 50.3%. All steps were repeated in the subgroup with any biopsy Gleason pattern 5, to predict RP Gleason pattern ≤4 + 4. Here, a second nomogram (n = 2315) yielded 68.0% accuracy, maximal departures from ideal prediction of ±5.7%, and virtually the same DCA pattern as the main nomogram.

Conclusions: Downgrading affects half of all high-risk PCa patients. Its presence may be predicted accurately and may help with better treatment planning.

Patient Summary: Downgrading occurs in every second high-risk prostate cancer patients. The nomograms developed by us can predict these probabilities accurately.
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http://dx.doi.org/10.1016/j.euf.2021.07.008DOI Listing
July 2021

The effect of race on stage at presentation and survival in upper tract urothelial carcinoma.

Urol Oncol 2021 Nov 27;39(11):788.e7-788.e13. Epub 2021 Jul 27.

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

Background The effect of racial/ethnic group on survival in upper tract urothelial carcinoma (UTUC) is unknown. We tested this concept in non-metastatic UTUC patients treated with radical nephroureterectomy (RNU) and hypothesized that important differences may exist according to racial/ethnic groups. Material and Methods We relied on the Surveillance Epidemiology and End Results database (2004-2016). We relied on Propensity-score matching (ratio 1:4). Subsequently, cumulative incidence plots and multivariable competing risks regression models (CRR) addressed cancer-specific mortality (CSM). Results Of 9129 assessable patients, 7454 (81.7%) were Caucasian vs. 665 (7.3%) Hispanic vs. 584 (6.4%) Asian vs. 426 (4.7%) African-American. No statistically significant differences were recorded for tumor grade or T-stage, between all racial/ethnic groups. However, within patents who received lymph-node dissection (n = 2694, 29.5%), Asians exhibited the highest rate of more than 2 positive lymph nodes at RNU (19.0%, followed by 17.1% African-Americans, 15.0% Caucasians and 12.6% Hispanics, P < 0.001). After PS-matching and multivariable CRR, Asian race/ethnicity independently predicted higher CSM, relative to Caucasians (Hazard ratio: 1.29, P < 0.01). No statistically significant differences according to CSM was recorded in the remaining races/ethnicities comparisons (all P ≥ 0.1) Conclusion Important CSM differences may exist according to race/ethnicity in non-metastatic UTUC patients treated with RNU. However, these differences only apply to Asian patients, who account for 6% of the overall non-metastatic UTUC cohort treated with RNU. In consequence, in clinical practice Asian patients should be given particular attention with the intent of reducing the CSM disadvantage that cannot be clearly explained by stage and/or grade disadvantage at diagnosis.
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http://dx.doi.org/10.1016/j.urolonc.2021.07.001DOI Listing
November 2021

Assessment of the optimal number of positive biopsy cores to discriminate between cancer-specific mortality in high-risk versus very high-risk prostate cancer patients.

Prostate 2021 Oct 26;81(14):1055-1063. Epub 2021 Jul 26.

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

Background: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa.

Methods: Within Surveillance, Epidemiology, and End Results database (2010-2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2-≥12) were tested in Kaplan-Meier, cumulative incidence, and multivariable Cox and competing risks regression models.

Results: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut-off (high-risk vs. very high-risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high-risk PCa.

Conclusions: The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice.
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http://dx.doi.org/10.1002/pros.24202DOI Listing
October 2021

The complete mitochondrial genome of Chinese minnow () and its phylogenetic analyses.

Mitochondrial DNA B Resour 2021 5;6(8):2177-2179. Epub 2021 Jul 5.

School of Marine Science, Ningbo University, Ningbo, China.

The complete mitochondrial genome can provide novel insights into understanding the mechanism underlying mitogenome evolution. In the present study, the whole mitochondrial genome of was determined to 16608 bp (GenBank accession No: MW057563), including 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region. The overall base composition was 28.62% A, 27.23% T, 26.31% C and 17.84% G, with a total A + T content of 55.85%. The Maximum Likelihood tree showed that the phylogenetic relationship is closer between and than the other species. The whole mitogenome of this species will be useful for the future animal evolutionary, phylogenetic relationship, and genomic studies in the genus .
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http://dx.doi.org/10.1080/23802359.2021.1875921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266249PMC
July 2021

Increasing rates of NCCN high and very high-risk prostate cancer versus number of prostate biopsy cores.

Prostate 2021 Sep 29;81(12):874-881. Epub 2021 Jun 29.

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

Background: Recently, an increase in the rates of high-risk prostate cancer (PCa) was reported. We tested whether the rates of and low, intermediate, high and very high-risk PCa changed over time. We also tested whether the number of prostate biopsy cores contributed to changes rates over time.

Methods: Within the Surveillance, Epidemiology and End Results (SEER) database (2010-2015), annual rates of low, intermediate, high-risk according to traditional National Comprehensive Cancer Network (NCCN) and high versus very high-risk PCa according to Johns Hopkins classification were tabulated without and with adjustment for the number of prostate biopsy cores.

Results: In 119,574 eligible prostate cancer patients, the rates of NCCN low, intermediate, and high-risk PCa were, respectively, 29.7%, 47.8%, and 22.5%. Of high-risk patients, 39.6% and 60.4% fulfilled high and very high-risk criteria. Without adjustment for number of prostate biopsy cores, the estimated annual percentage changes (EAPC) for low, intermediate, high and very high-risk were respectively -5.5% (32.4%-24.9%, p < .01), +0.5% (47.6%-48.4%, p = .09), +4.1% (8.2%-9.9%, p < .01), and +8.9% (11.8%-16.9%, p < .01), between 2010 and 2015. After adjustment for number of prostate biopsy cores, differences in rates over time disappeared and ranged from 29.8%-29.7% for low risk, 47.9%-47.9% for intermediate risk, 8.9%-9.0% for high-risk, and 13.6%-13.6% for very high-risk PCa (all p > .05).

Conclusions: The rates of high and very high-risk PCa are strongly associated with the number of prostate biopsy cores, that in turn may be driven by broader use magnetic resonance imaging (MRI).
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http://dx.doi.org/10.1002/pros.24184DOI Listing
September 2021

Validation of the STAR-CAP Clinical Prognostic System for Predicting Biochemical Recurrence, Metastasis, and Cancer-specific Mortality After Radical Prostatectomy in a European Cohort.

Eur Urol 2021 10 23;80(4):400-404. Epub 2021 Jun 23.

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

The proposed international staging collaboration for cancer of the prostate (STAR-CAP) clinical prognostic system for prostate cancer predicts cancer-specific mortality (CSM) for patients for whom active treatment, such as radical prostatectomy (RP), is planned. Until now, no validation of STAR-CAP has been performed. We retrospectively analyzed data from our institutional database for 19 552 patients treated with RP between 1992 and 2015. We applied the STAR-CAP point assignment criteria to calculate total individual scores and then classified patients according to the STAR-CAP stage groups ranging from IA (lowest risk) to IIIC (highest risk). We evaluated biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS), and cancer-specific survival (CSS) stratified by STAR-CAP stage groups over 10 yr, calculated the area under the receiver operating characteristics curve (AUC), and performed decision curve analyses to assess the ability of STAR-CAP to predict these outcomes after fitting the data from our single-institution data set. STAR-CAP performed well in stratifying individual survival outcomes for BCR-free survival, MFS, and CSS for each stage group in Kaplan-Meier analyses (p < 0.001 between groups). The AUC for prediction of BCR, metastasis, and CSM at 10 yr was 0.73, 0.84, and 0.75, respectively. Our findings validate the performance of STAR-CAP for European patients treated with RP. PATIENT SUMMARY: We validated the STAR-CAP system for predicting cancer outcomes after removal of the prostate. Our results show that the system performs well and could help in counseling patients with prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.06.008DOI Listing
October 2021

High-risk Surgically Resected Renal Cell Carcinoma: Is There a Role for Adjuvant VEGF-TKI Inhibitors?

Curr Probl Cancer 2021 Dec 5;45(6):100759. Epub 2021 Jun 5.

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.

The indications for adjuvant vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) agents after curative intent nephrectomy for renal cell carcinoma are still a matter of debate. The ASSURE, PROTECT and ATLAS trials have failed to meet their primary end-points. Conversely, S-TRAC has shown a disease free survival (DFS) benefit. To date, meta-analyses have repeatedly proved the absence of a clinical benefit, in term of DFS and overall survival (OS). Nevertheless, the results of the SORCE trial have been recently released and might add valuable information. We pooled the results of all five reported trials testing for any potential DFS and OS benefits associated with VEGF-TKI use. Interestingly, for pooled DFS we found a marginal positive hazard ratio (HR) of 0.92 (95% confidence interval [CI] 0.85-1.00; P-value = 0.049) in favor of adjuvant VEGF-TKI agents. This benefit was more pronounced for DFS in the sub-groups of only high-risk patients (HR: 0.89, 95% CI 0.80-0.99; P-value = 0.026), but less pronounced in clear-cell only subgroup (HR 0.92, 95% CI: 0.85-1.00; P-value = 0.044). Overall survival benefit was instead not reached. However, pooled relative risk for high-grade (grade ≥3 according to CTCAE classification) adverse events was irremediably high, 2.56 (95% CI: 2.15-3.04; P-value < 0.001). Given the marginal benefit in terms of DFS and the drawback of high-grade adverse events, even after the SORCE trial publication, adjuvant VEGF-TKIs therapy cannot be considered in the whole group of patients with non-metastatic high-risk renal cell carcinoma after surgery.
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http://dx.doi.org/10.1016/j.currproblcancer.2021.100759DOI Listing
December 2021
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