Publications by authors named "Alberto Briganti"

1,096 Publications

  • Page 1 of 1

Does previous prostate surgery affect multiparametric magnetic resonance imaging accuracy in detecting clinically significant prostate cancer? Results from a single institution series.

Prostate 2022 May 10. Epub 2022 May 10.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS San Raffaele Hospital, Milan, Italy.

Background: Multiparametric MRI (mpMRI) has demonstrated high diagnostic accuracy for clinically significant PCa (csPCa). However, the accuracy of this test in men that received a previous prostatic surgery is still controversial. We aimed at assessing the effect of previous prostatic surgery on the detection of csPCa in a tertiary referral center.

Method: We relied on a cohort of 311 men with a positive mpMRI (prostate imaging - reporting and data system [PI-RADS] ≥ 3) who underwent a targeted (TBx) plus concomitant systematic random biopsy (SBx) at a single tertiary referral center between 2017 and 2020. The study outcome was to compare the detection of csPCa (Gleason score ≥ 3 + 4) between the two groups (no previous prostate surgery [Group 1] vs. previous prostate surgery [Group 2]). Multivariable logistic regression analysis (MVA) was used to assess the relationship between previous prostate surgery and the detection of csPCa at TBx, after taking into account potential clinical confounders.

Results: Overall, 24 (8%) patients received a previous prostate surgery before undergoing mpMRI. Median prostate-specific antigen density was 0.15 versus 0.08 ng/ml/cc, in Group 1 versus 2, respectively. The most frequent finding at mpMRI was in Group 1 versus 2, PI-RADS 4 (55%) versus PI-RADS 3 and 4 (42% each). The majority of patients were biopsy naïve in both Groups 1 (66%) and 2 (71%). The overall detection of csPCa in Group 1 versus 2 was 83% versus 75%, respectively. Differently, the detection of csPCa at TBx in Groups 1 versus 2 was 76% versus 71%, respectively. At MVA, previous prostate surgery (odds ratio: 0.65; p = 0.02) was significantly associated with lower csPCa detection at TBx, after accounting for potential confounders.

Conclusion: The presence of previous prostate surgery significantly decreases the accuracy of mpMRI in detecting csPCa. These results should be taken into account when assessing patients with a history of prostatic surgery and a suspicious lesion at mpMRI, to better select those who might avoid an unnecessary biopsy.
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http://dx.doi.org/10.1002/pros.24368DOI Listing
May 2022

Radiation therapy compared to radical prostatectomy as first-line definitive therapy for patients with high-risk localised prostate cancer: An updated systematic review and meta-analysis.

Arab J Urol 2022 30;20(2):71-80. Epub 2022 Mar 30.

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

Objective: To present an update of the available literature on external beam radiation therapy (EBRT) with or without brachytherapy (BT) compared to radical prostatectomy (RP) for patients with high-risk localised prostate cancer (PCa).

Methods: We conducted a systematic review and meta-analysis of the literature assessing the survival outcomes in patients with high-risk PCa who received EBRT with or without BT compared to RP as the first-line therapy with curative intent. We queried PubMed and Web of Science database in January 2021. Moreover, we used random or fixed-effects meta-analytical models in the presence or absence of heterogeneity per the statistic, respectively. We performed six meta-analyses for overall survival (OS) and cancer-specific survival (CSS).

Results: A total of 27 studies were selected with 23 studies being eligible for both OS and CSS. EBRT alone had a significantly worse OS and CSS compared to RP (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.16-1.65; and HR 1.55, 95% CI 1.25-1.93). However, there was no difference in OS (HR 1.1, 95% CI 0.76-1.34) and CSS (HR 0.69, 95% CI 0.45-1.06) between EBRT plus BT compared to RP.

Conclusion: While cancer control affected by EBRT alone seems inferior to RP in patients with high-risk PCa, BT additive to EBRT was not different from RP. These data support the need for BT in addition to EBRT as part of multimodal RT for high-risk PCa. ADT: androgen-deprivation therapy; BT: brachytherapy; CSS: cancer-specific survival; HR: hazard ratio; MFS, metastatic-free survival; MOOSE: Meta-analyses of Observational Studies in Epidemiology; OR: odds ratio; OS: overall survival; PCa: prostate cancer; RR: relative risk; RP: radical prostatectomy; RCT: randomised controlled trials; (EB)RT: (external beam) radiation therapy.
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http://dx.doi.org/10.1080/2090598X.2022.2026010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067961PMC
March 2022

Life expectancy in metastatic urothelial bladder cancer patients according to race/ethnicity.

Int Urol Nephrol 2022 May 4. Epub 2022 May 4.

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

Purpose: to compare observed overall survival vs age-adjusted lifetable (LT) derived life expectancy (LE) in metastatic urothelial bladder cancer (MBCa) patients according to race/ethnicity.

Methods: We identified Caucasian, African American, Hispanic/Latino and Asian metastatic urothelial bladder cancer patients from 2004 to 2011 within the Surveillance, Epidemiology and End Results database. Social Security Administration tables were used to compute 5 year LE. LT-derived LE was compared to observed overall survival OS. Additionally, we relied on Poisson regression plots to display cancer-specific mortality (CSM) relative to other-cause mortality (OCM) for each race/ethnicity.

Results: Overall, 2286 MBCa patients were identified. Of those, 1800 (79%) were Caucasian vs 212 (9.3%) African American vs 189 (8.3%) Hispanic/Latino vs 85 (3.7%) Asians. The median age at diagnosis was 71 years for Asians vs 70 for Caucasians vs 67 for Hispanic/Latinos vs 67 for African Americans. African Americans showed the biggest difference between observed OS and LT-predicted LE at five years (- 83.8%), followed by Hispanic/Latinos (- 81%), Caucasians (- 77%) and Asian patients (- 69%). In Poisson regression plots, Hispanic/Latinos displayed the highest cancer-specific mortality rate (88%), while African/Americans showed the highest other cause mortality rate (12%). Conversely, Asian patients displayed the lowest CSM rate (83%) and second lowest OCM rate (7%).

Conclusions: African Americans showed the least favorable survival profile in MBCa, despite being youngest at diagnosis. Contrarily, Asians displayed the best survival profile in MBCa, despite being oldest at diagnosis.
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http://dx.doi.org/10.1007/s11255-022-03221-5DOI Listing
May 2022

Oncologic Surveillance After Radical Nephroureterectomy for High-risk Upper Tract Urothelial Carcinoma.

Eur Urol Oncol 2022 Apr 30. Epub 2022 Apr 30.

Department of Urology, Vita-Salute San Raffaele University, Milan, Italy.

Background: The appropriate surveillance protocol after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is still poorly addressed.

Objective: To evaluate the appropriate intensity and duration of oncologic surveillance following RNU, according to a prior history of bladder cancer (BCa).

Design, Setting, And Participants: We identified 1378 high-risk UTUC patients, according to the European Association of Urology (EAU) guidelines, from a prospectively maintained database involving eight European referral centers. Surveillance protocol was based on cystoscopies and cross-sectional imaging, as per the EAU guidelines.

Outcome Measurements And Statistical Analysis: First, we evaluated the noncumulative risk of bladder and other-site recurrences (including distant metastasis and locoregional relapse) against the follow-up time points, as suggested by the current EAU guidelines. Second, in an effort to identify the time points when the risk of other-cause mortality (OCM) exceeded that of recurrence and follow-up might be discontinued, we relied on adjusted Weibull regression.

Results And Limitations: The median follow-up was 4 yr. A total of 427 and 951 patients with and without a prior BCa history, respectively, were considered. At 5-yr, the time point after which cystoscopies should be performed semiannually, the bladder recurrence risk was 10%; at 4 yr, the bladder recurrence risk was 13%. At 2 yr, the time point after which imaging should be obtained semiannually, the nonbladder recurrence risk was 42% in case of nonprior BCa and 47% in case of prior BCa; at 4 yr, the nonbladder recurrence risk was 23%. Among patients without a prior BCa history, individuals younger than 60 yr should continue both cystoscopies and imaging beyond 10 yr from RNU, 70-79-yr-old patients should continue only imaging beyond 10 yr, while patients older than 80 yr might discontinue oncologic surveillance because of an increased risk of OCM. Limitations include the fact that patients were treated and surveilled over a relatively long period of time.

Conclusions: We suggest intensifying the frequency of imaging to semiannual till the 4th year after RNU, the time point after which the risk of recurrence was almost halved. Cystoscopies could be obtained annually from the 4th year given a similar risk of recurrence at 4 and 5 yr after RNU. Oncologic surveillance could be discontinued in some cases in the absence of a prior BCa history.

Patient Summary: In this study, we propose a revision of the current guidelines regarding surveillance protocols following radical nephroureterectomy. We also evaluated whether oncologic surveillance for high-risk upper tract urothelial carcinoma could be discontinued and, if so, in what circumstances.
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http://dx.doi.org/10.1016/j.euo.2022.04.003DOI Listing
April 2022

Neoadjuvant chemotherapy does not increase peri-operative morbidity following radical cystectomy.

World J Urol 2022 Apr 30. Epub 2022 Apr 30.

Department of Urology, Institut Mutualiste Montsouris and Université Paris Descartes, Paris, France.

Objective: To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa).

Materials And Methods: We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period.

Results: Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p < 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018.

Conclusion: This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit.
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http://dx.doi.org/10.1007/s00345-022-04012-4DOI Listing
April 2022

Intensification of Systemic Therapy in Addition to Definitive Local Treatment in Nonmetastatic Unfavourable Prostate Cancer: A Systematic Review and Meta-analysis.

Eur Urol 2022 Apr 21. Epub 2022 Apr 21.

Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France.

Context: Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC).

Objective: To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC.

Evidence Acquisition: We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes.

Evidence Synthesis: We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile.

Conclusions: Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT.

Patient Summary: Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.
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http://dx.doi.org/10.1016/j.eururo.2022.03.031DOI Listing
April 2022

Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021.

Eur Urol 2022 Apr 18. Epub 2022 Apr 18.

Department of Oncology and Radiotherapy, Innlandet Hospital Trust, Gjøvik, Norway.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence.

Objective: To present the voting results from APCCC 2021.

Design, Setting, And Participants: The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions.

Outcome Measurements And Statistical Analysis: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process.

Results And Limitations: The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material.

Conclusions: These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials.

Patient Summary: The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making.
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http://dx.doi.org/10.1016/j.eururo.2022.04.002DOI Listing
April 2022

Survival trends in chemotherapy exposed metastatic bladder cancer patients and chemotherapy effect across different age, sex, and race/ethnicity.

Urol Oncol 2022 Apr 14. Epub 2022 Apr 14.

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

Purpose: To test for survival differences in metastatic urothelial carcinoma of the urinary bladder (mUCUB) patients, according to years of diagnosis, age, sex, and race/ethnicity over time and for the effect of chemotherapy on overall mortality (OM).

Materials And Methods: Within the Surveillance, Epidemiology, and End Results (2000-2016), we identified 6860 mUCUB patients. Of those, 3,249 were exposed to chemotherapy. Kaplan-Meier plots and Cox regression models focused on OM. First, we tested the effect of years of diagnosis (historical [2000-2005] vs. intermediate [2006-2011] vs. contemporary [2012-2016]) in chemotherapy exposed mUCUB patients. Second, we tested the effect of chemotherapy in all mUCUB patients.

Results: In chemotherapy exposed mUCUB patients according to historical vs. intermediate vs. contemporary years, median overall survival was 11 vs. 13 vs. 14 months respectively, which translated into hazard ratios (HR) of 0.86 (P = 0.005) and 0.75 (P < 0.001) in intermediate and contemporary vs. historical, respectively. Subgroup analyses in <70 years old, males and Caucasians were in agreement regarding statistically significant differences between historical vs. intermediate vs. contemporary, respectively. In multivariable Cox regression models fitted in the entire mUCUB cohort, chemotherapy exposure reduced OM (HR: 0.46; P < 0.001). Virtually the same results were recorded in age, sex, and race/ethnicity subgroups analyses.

Conclusions: Contemporary chemotherapy exposed mUCUB patients exhibited better survival than their historical and intermediate counterparts. Chemotherapy reduced mortality by half, across all patient types.
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http://dx.doi.org/10.1016/j.urolonc.2022.03.014DOI Listing
April 2022

Contemporary seminal vesicle invasion rates in NCCN high-risk prostate cancer patients.

Prostate 2022 Apr 11. Epub 2022 Apr 11.

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

Background: Contemporary seminal vesicle invasion (SVI) rates in National Cancer Comprehensive Network (NCCN) high-risk prostate cancer (PCa) patients are not well known but essential for treatment planning. We examined SVI rates according to individual patient characteristics for purpose of treatment planning.

Materials And Methods: Within Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), 4975 NCCN high-risk patients were identified. In the development cohort (SEER geographic region of residence: South, North-East, Mid-West, n = 2456), we fitted a multivariable logistic regression model predicting SVI. Its accuracy, calibration, and decision curve analyses (DCAs) were then tested versus previous models within the external validation cohort (SEER geographic region of residence: West, n = 2519).

Results: Out of 4975 patients, 28% had SVI. SVI rate ranged from 8% to 89% according to clinical T stage, prostate-specific antigen (PSA), biopsy Gleason Grade Group and percentage of positive biopsy cores. In the development cohort, these variables were independent predictors of SVI. In the external validation cohort, the current model achieved 77.6% accuracy vs 73.7% for Memorial Sloan Kettering Cancer Centre (MSKCC) vs 68.6% for Gallina et al. Calibration was better than for the two alternatives: departures from ideal predictions were 6.0% for the current model vs 9.8% for MSKCC vs 38.5% for Gallina et al. In DCAs, the current model outperformed both alternatives. Finally, different nomogram cutoffs allowed to discriminate between low versus high SVI risk patients.

Conclusions: More than a quarter of NCCN high-risk PCa patients harbored SVI. Since SVI positivity rate varies from 8% to 89%, the currently developed model offers a valuable approach to distinguish between low and high SVI risk patients.
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http://dx.doi.org/10.1002/pros.24350DOI Listing
April 2022

What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021.

Eur Urol 2022 Feb 17. Epub 2022 Feb 17.

University of British Columbia, Vancouver, British Columbia, Canada.

Patients with advanced prostate cancer (APC) may be at greater risk for severe illness, hospitalisation, or death from coronavirus disease 2019 (COVID-19) due to male gender, older age, potential immunosuppressive treatments, or comorbidities. Thus, the optimal management of APC patients during the COVID-19 pandemic is complex. In October 2021, during the Advanced Prostate Cancer Consensus Conference (APCCC) 2021, the 73 voting members of the panel members discussed and voted on 13 questions on this topic that could help clinicians make treatment choices during the pandemic. There was a consensus for full COVID-19 vaccination and booster injection in APC patients. Furthermore, the voting results indicate that the expert's treatment recommendations are influenced by the vaccination status: the COVID-19 pandemic altered management of APC patients for 70% of the panellists before the vaccination was available but only for 25% of panellists for fully vaccinated patients. Most experts (71%) were less likely to use docetaxel and abiraterone in unvaccinated patients with metastatic hormone-sensitive prostate cancer. For fully vaccinated patients with high-risk localised prostate cancer, there was a consensus (77%) to follow the usual treatment schedule, whereas in unvaccinated patients, 55% of the panel members voted for deferring radiation therapy. Finally, there was a strong consensus for the use of telemedicine for monitoring APC patients. PATIENT SUMMARY: In the Advanced Prostate Cancer Consensus Conference 2021, the panellists reached a consensus regarding the recommendation of the COVID-19 vaccine in prostate cancer patients and use of telemedicine for monitoring these patients.
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http://dx.doi.org/10.1016/j.eururo.2022.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849852PMC
February 2022

Metastasis Within Three Years from Radical Nephroureterectomy as a Potential Surrogate for Overall Survival.

Clin Genitourin Cancer 2022 Mar 10. Epub 2022 Mar 10.

Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland.

Introduction: The only phase III trial that evaluated the role of adjuvant chemotherapy following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) was terminated early. Thus, eventual overall survival (OS) surrogacy, as per Prentice, cannot be assessed in this setting. We aimed to identify an intermediate clinical endpoint (ICE) that could serve as an OS surrogate after RNU for UTUC.

Patients And Methods: We retrospectively analyzed 823 high-grade UTUC patients treated with RNU at 8 tertiary referral centers. We explored the role of any recurrence (aR), defined as recurrence in the urinary tract or in the resection bed as well the presence of distant metastasis (DM), defined as metastatic disease outside the urinary tract and regional lymph nodes, on OS through a time-varying Cox regression analyses fitted at the landmark points of 1, 2, 3, and 4 years from RNU. Models' discrimination was assessed using Harrell's c index, after internal validation.

Results: Median follow-up for survivors was 5.6 years (interquartile range: 2.0-8.8). Overall, 391 and 212 patients experienced aR and DM, respectively. In a time-varying model, aR and DM were predictors of OS: hazard ratio [HR]:1.20, 95% confidence interval [CI]: 1.13-1.28 (P < .001) and HR:1.26, 95% CI: 1.18-1.34 (P < .001), respectively. Progression to DM within 3 years from RNU was the most informative ICE for predicting OS (c index: 0.81; HR: 4.40; 95%CI: 2.45-7.92; P < .001), compared to DM within 1, 2, and 4 years (c indexes: 0.74, 0.76, and 0.78, respectively). Progression to DM within 3 years from RNU was further found superior for predicting OS compared to aR at any landmark points.

Conclusions: Progression to DM within 3 years represents a potential OS surrogate for surgically-treated UTUC. This information could help in patient counseling, future study design and expedite results release of ongoing randomized controlled trials.
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http://dx.doi.org/10.1016/j.clgc.2022.03.007DOI Listing
March 2022

Diagnostic and prognostic factors in patients with prostate cancer: a systematic review.

BMJ Open 2022 Apr 4;12(4):e058267. Epub 2022 Apr 4.

Department of Translational Medicine, Lund University, Malmö, Sweden.

Objectives: As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa).

Design: We performed a systematic review to identify validated and non-validated studies.

Data Sources: MEDLINE, Embase and the Cochrane Library were searched on 21 January 2020.

Eligibility Criteria: Only quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded.

Data Extraction And Synthesis: After initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2.

Results: The search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability.

Conclusion: Most of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies.

Ethics And Dissemination: There are no ethical implications.
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http://dx.doi.org/10.1136/bmjopen-2021-058267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981333PMC
April 2022

Grade and stage misclassification in intermediate unfavorable-risk prostate cancer radiotherapy candidates.

Prostate 2022 Apr 1. Epub 2022 Apr 1.

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

Background: We tested for upgrading (Gleason grade group [GGG] ≥ 4) and/or upstaging to non-organ-confined stage ([NOC] ≥ pT3/pN1) in intermediate unfavorable-risk (IU) prostate cancer (PCa) patients treated with radical prostatectomy, since both change the considerations for dose and/or type of radiotherapy (RT) and duration of androgen deprivation therapy (ADT).

Methods: We relied on Surveillance, Epidemiology, and End Results (2010-2015). Proportions of (a) upgrading, (b) upstaging, or (c) upgrading and/or upstaging were tabulated and tested in multivariable logistic regression models.

Results: We identified 7269 IU PCa patients. Upgrading was recorded in 479 (6.6%) and upstaging in 2398 (33.0%), for a total of 2616 (36.0%) upgraded and/or upstaged patients, who no longer fulfilled the IU grade and stage definition. Prostate-specific antigen, clinical stage, biopsy GGG, and percentage of positive cores, neither individually nor in multivariable logistic regression models, discriminated between upgraded and/or upstaged patients versus others.

Conclusions: IU PCa patients showed very high (36%) upgrading and/or upstaging proportion. Interestingly, the overwhelming majority of those were upstaged to NOC. Conversely, very few were upgraded to GGG ≥ 4. In consequence, more than one-third of IU PCa patients treated with RT may be exposed to suboptimal dose and/or type of RT and to insufficient duration of ADT, since their true grade and stage corresponded to high-risk PCa definition, instead of IU PCa. Data about magnetic resonance imaging were not available but may potentially help with better stage discrimination.
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http://dx.doi.org/10.1002/pros.24349DOI Listing
April 2022

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

J Urol 2022 Mar 29:101097JU0000000000002680. Epub 2022 Mar 29.

Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

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http://dx.doi.org/10.1097/JU.0000000000002680DOI Listing
March 2022

Radiomic and gEnomic approaches for the enhanced DIagnosis of clear cell REnal Cancer (REDIRECt): a translational pilot methodological study.

Transl Androl Urol 2022 Feb;11(2):149-158

Unit of Urology, Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Background: The combination of radiomic and transcriptomic approaches for patients diagnosed with small clear-cell renal cell carcinoma (ccRCC) might improve decision making. In this pilot and methodological study, we investigate whether imaging features obtained from computed tomography (CT) may correlate with gene expression patterns in ccRCC patients.

Methods: Samples from 6 patients who underwent partial nephrectomy for unilateral non-metastatic ccRCC were included in this pilot cohort. Transcriptomic analysis was conducted through RNA-sequencing on tumor samples, while radiologic features were obtained from pre-operative 4-phase contrast-enhanced CT. To evaluate the heterogeneity of the transcriptome, after a 1,000 re-sampling via bootstrapping, a first Principal Component Analyses (PCA) were fitted with all transcripts and a second ones with transcripts deriving from a list of 369 genes known to be associated with ccRCC from The Cancer Genome Atlas (TCGA). Significant pathways in each Principal Components for the 50 genes with the highest loadings absolute values were assessed with pathways enrichment analysis. In addition, Pearson's correlation coefficients among radiomic features themselves and between radiomic features and transcripts expression values were computed.

Results: The transcriptomes of the analysed samples showed a high grade of heterogeneity. However, we found four radiogenomic patterns, in which the correlation between radiomic features and transcripts were statistically significant.

Conclusions: We showed that radiogenomic approach is feasible, however its clinical meaning should be further investigated.
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http://dx.doi.org/10.21037/tau-21-713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899146PMC
February 2022

Effect of Neoadjuvant Chemotherapy on Complications, in-Hospital Mortality, Length of Stay and Total Hospital Costs in Bladder Cancer Patients Undergoing Radical Cystectomy.

Cancers (Basel) 2022 Feb 26;14(5). Epub 2022 Feb 26.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC H4A 3J1, Canada.

Background: To test for differences in complication rates, in-hospital mortality, length of stay (LOS) and total hospital costs (THCs) in patients treated with neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC).

Methods: Within the National (Nationwide) Inpatient Sample (NIS) database (2016-2019), we identified RC-treated, non-metastatic, lymph-node negative bladder cancer patients, stratified by NAC status. Trend analyses, multivariable logistic, multivariable Poisson and multivariable linear regression models were used.

Results: We identified 4347 RC-treated bladder cancer patients. Of those, 805 (19%) received NAC prior to RC. Overall, complications rates did not differ (65 vs. 66%; = 0.7). However, NAC patients harbored lower rates of surgical site (6 vs. 9%), cardiac (13 vs. 19%) and genitourinary (5.5 vs. 9.7%) complications. In-hospital mortality (<1.7 vs. 1.8%) and LOS (6 vs. 7 days) was lower in NAC patients (all < 0.05). Moreover, NAC was an independent predictor of shorter LOS in multivariable Poisson regression models (Risk ratio: 0.86; < 0.001) and an independent predictor for higher THCs in multivariable linear regression models (Odds ratio: 1474$; = 0.02).

Conclusion: NAC was not associated with higher complication rates and in-hospital mortality. Contrary, NAC was associated with shorter LOS, yet moderately higher THCs. The current analysis suggests no detriment from NAC in the context of RC.
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http://dx.doi.org/10.3390/cancers14051222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909906PMC
February 2022

Up- and downgrading in single intermediate-risk positive biopsy core prostate cancer.

Prostate Int 2022 Mar 26;10(1):21-27. Epub 2022 Jan 26.

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

Background: Up- and/or downgrading rates in single intermediate-risk positive biopsy core are unknown.

Methods: We identified single intermediate-risk (Gleason grade group (GGG) 2/GGG3) positive biopsy core prostate cancer patients (≤ cT2c and PSA ≤ 20 ng/mL) within the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). Subsequently, separate uni- and multivariable logistic regression models tested for independent predictors of up- and downgrading.

Results: Of 1,328 assessable patients with single core positive intermediate-risk prostate cancer at biopsy, 972 (73%) harbored GGG2 versus 356 (27%) harbored GGG3. Median PSA (5.5 vs 5.7;  = 0.3), median age (62 vs 63 years;  = 0.07) and cT1-stage (77 vs 75%;  = 0.3) did not differ between GGG2 and GGG3 patients. Of individuals with single GGG2 positive biopsy core, 191 (20%) showed downgrading to GGG1 versus 35 (4%) upgrading to GGG4 or GGG5 at RP. Of individuals with single GGG3 positive biopsy core, 36 (10%) showed downgrading to GGG1 versus 42 (12%) significant upgrading to GGG4 or GGG5 at RP. In multivariable logistic regression models, elevated PSA (10-20 ng/mL) was an independent predictor of upgrading to GGG4/GGG5 in single GGG3 positive biopsy core patients (OR:2.89; 95%-CI: 1.31-6.11;  = 0.007).

Conclusion: In single GGG2 positive biopsy core patients, downgrading was four times more often recorded compared to upgrading. Conversely, in single GGG3 positive biopsy core patients, up- and downgrading rates were comparable and should be expected in one out of ten patients.
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http://dx.doi.org/10.1016/j.prnil.2022.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866049PMC
March 2022

The impact of lymphovascular invasion in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma: An extensive updated systematic review and meta-analysis.

Urol Oncol 2022 Jun 28;40(6):243-261. Epub 2022 Feb 28.

Unit of Oncologic Minimally-Invasive Urology and Andrology, Department of Experimental and Clinical Medicine, Careggi Hospital, University of Florence, Florence, Italy.

Patients with upper tract urothelial carcinoma (UTUC) often have a delayed diagnosis and by then, present with advanced disease which has been shown to be associated with lymphovascular invasion (LVI). It has been suggested to be involved in the metastatic cascade of the disease. In this review, we provide an extensive up-to-date summary of the current knowledge about the prognostic impact of LVI in patients undergoing radical nephroureterectomy (RNU). A systematic search of PubMed/MEDLINE, Scopus, EMBASE, and Web of Science for all reports published from 2010 through 2021 was performed. We performed pooled analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of series that evaluated LVI as a prognostic factor in adults with UTUC who underwent RNU. The assessed oncological outcomes were disease recurrence, cancer-specific and overall survival. A meta-regression analysis was used to explore potential heterogeneity. A total of 58 series met the eligibility criteria for qualitative and quantitative synthesis. We included 29,829 patients, ranging from 101 to 2492 per study. All series were retrospective. LVI was present in 7,818 patients (26.2%). The median age of the patients was 69 years and the median follow-up was 40 months. In 40 of 58 studies (68.9%), adjuvant chemotherapy was given. The pooled HRs show that LVI predicts a greater risk of recurrence of the disease (pooled HR 1.43, 95% CI: 1.31-1.55, P = 0.000; I = 76.3%), and decreases cancer-specific survival (pooled HR 1.53, 95% CI: 1.41-1.66, P = 0.000; I = 72.3%) and overall survival (HR 1.56, 95% CI 1.45-1.69, P = 0.000; I = 62.9%). It can be concluded that LVI is a common histologic pattern in surgical specimen in patients undergoing RNU for UTUC. LVI predicts a greater risk of recurrence and mortality, thus it should be carefully assessed in clinical practice to determine prognosis, and for optimal decision-making within the concept of personalized therapies.
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http://dx.doi.org/10.1016/j.urolonc.2022.01.014DOI Listing
June 2022

Diagnostic accuracy of preoperative lymph node staging of bladder cancer according to different lymph node locations: A multicenter cohort from the European Association of Urology - Young Academic Urologists.

Urol Oncol 2022 May 27;40(5):195.e27-195.e35. Epub 2022 Feb 27.

Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland; Clinica Luganese Moncucco, Lugano, Switzerland; Clinica S.Anna, Swiss Medical Group, Sorengo, Switzerland; Clinica Santa Chiara, Locarno, Switzerland.

Background: The preoperative lymph node (LN) staging of bladder cancer (BCa) addresses the subsequent therapeutic strategy and influences patient's prognosis. However, sparce evidence exists regarding the accuracy of conventional cross-sectional imaging, such as computed tomography or magnetic resonance imaging, in correctly detect LN status. We aimed to assess the diagnostic accuracy of conventional cross-sectional imaging in detecting preoperative LN involvement among BCa patients treated with radical cystectomy and pelvic lymph node dissection.

Methods: We retrospectively analyzed data of 1,104 patients who underwent preoperative LN staging with computed tomography or magnetic resonance imaging and subsequent radical cystectomy with pelvic lymph node dissection for BCa between 1997 and 2017 at three tertiary referral centers. Patients receiving neoadjuvant chemotherapy were excluded. We assessed the concordance between clinical (cN) and pathological LN (pN) status, defined as the accuracy of imaging in detecting LN involvement using pathological specimen as reference; concordance was expressed according to Cohen's kappa coefficient. Location-based sub-analyses were performed, distinguishing among external iliac, intern iliac, obturator, common iliac, presacral and paraaortic LNs.

Results: Among 870 cN0 patients, 68.9% were confirmed pN0 at pathological report; while among 234 cN+ patients, 50.5% were found with LN metastases at pathological specimen. Overall, conventional imaging showed slight concordance (64.9%) between cN and pN stages (sensitivity: 30%; specificity: 84%). At sub-analysis, no agreement between cN and pN status was found in each LN location, with the only exception of common iliac LNs with slight concordance (37.5%). Common iliac LNs achieved the highest sensitivity and positive likelihood ratio (15% and 2.4, respectively) compared to other LN locations.

Conclusions: Overall, preoperative cross-sectional imaging exhibited a slight concordance between cN and pN status. Our location-based sub-analyses showed unsatisfactory results in each LN location- Thus, nomograms combining morphological patterns with serological and clinicopathological features are urgently required.
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http://dx.doi.org/10.1016/j.urolonc.2022.01.002DOI Listing
May 2022

Radiation therapy after radical prostatectomy is associated with higher other-cause mortality.

Cancer Causes Control 2022 May 1;33(5):769-777. Epub 2022 Mar 1.

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

Purpose: To test the association between external beam radiotherapy (EBRT) after radical prostatectomy (RP) vs RP only on rates of other-cause mortality (OCM) in men with prostate cancer (PCa).

Patients And Methods: Within the 2004-2016 Surveillance, Epidemiology, and End Results database, we identified 181,849 localized PCa patients, of whom 168,041 received RP only vs 13,808 who received RP + EBRT. Cumulative incidence plots displayed OCM between RP vs RP + EBRT after propensity score matching for age, PSA, clinical T- and N-stages, and biopsy Gleason scores. Multivariable competing risks regression models addressed OCM, accounting prostate cancer-specific mortality (CSM) as a competing event. Stratifications were made according to low- vs intermediate- vs high-risk groups and additionally according to age groups of ≤ 60, 61-70, and ≥ 71 years, within each risk group.

Results: In low-, intermediate-, and high-risk patients, RP + EBRT rates were 2.7, 5.4 and 17.0%, respectively. After matching, 10-year OCM rates between RP and RP + EBRT were 7.7 vs 16.2% in low-, 9.4 vs 13.6% in intermediate-, and 11.4 vs 13.5% in high-risk patients (all p < 0.001), which, respectively, resulted in multivariable HR of 2.1, 1.3, and 1.2 (all p < 0.001). In subgroup analyses, excess OCM was recorded in low-risk RP + EBRT patients of all age groups (all p ≤ 0.03), but only in the older age group in intermediate-risk patients (61-70 years, p = 0.03) and finally, only in the oldest age group in high-risk patients (≥ 71 years, p = 0.02).

Conclusion: Excess OCM was recorded in patients exposed to RT after RP. Its extent was most pronounced in low-risk patients, decreased in intermediate-risk patients, and was lowest in high-risk patients.
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http://dx.doi.org/10.1007/s10552-022-01564-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010398PMC
May 2022

Survival after radical prostatectomy versus radiation therapy in clinical node-positive prostate cancer.

Prostate 2022 05 28;82(6):740-750. Epub 2022 Feb 28.

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

Aim: To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa).

Materials And Methods: Within Surveillance, Epidemiology, End Results (SEER) (2004-2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 1:1 propensity score matching (PSM), Kaplan-Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model.

Results: Overall, RT patients were older, harbored higher prostate-specific antigen values, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3% versus 17%, and 6.1% versus 8% for RP versus RT (all p < 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52-0.78, p < 0.001), 0.66 (0.52-0.86, p < 0.001), 0.71 (0.5-1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46-0.66) for OM, and CRR yielded HRs of 0.49 (0.34-0.70) and 0.54 (0.36-0.79) for, respectively, CSM and OCM, all favoring RP (all p < 0.001).

Conclusions: RP may hold a CSM advantage over RT in cN1 PCa patients.
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http://dx.doi.org/10.1002/pros.24317DOI Listing
May 2022

Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.

World J Urol 2022 May 26;40(5):1167-1174. Epub 2022 Feb 26.

Department of Urology, Fundación Instituto Valenciano de Oncologia, Valencia, Spain.

Purpose: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa).

Methods: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy.

Results: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively).

Conclusion: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.
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http://dx.doi.org/10.1007/s00345-022-03958-9DOI Listing
May 2022

Variant histologies in bladder cancer: Does the centre have an impact in detection accuracy?

Urol Oncol 2022 Jun 23;40(6):273.e11-273.e20. Epub 2022 Feb 23.

Department of Urology, Policlinico San Martino Hospital, University of Genova, Genova, Italy.

Objective: To compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view.

Patients And Methods: Clinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient.

Results: A VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study.

Conclusions: Accuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment.
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http://dx.doi.org/10.1016/j.urolonc.2022.01.008DOI Listing
June 2022

Prostate Cancer: Is There Still a Role for Systematic Biopsies? Yes.

Eur Urol Open Sci 2022 Apr 10;38:10-11. Epub 2022 Feb 10.

Unit of Urology/Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.

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http://dx.doi.org/10.1016/j.euros.2021.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844839PMC
April 2022

Non-organ confined stage and upgrading rates in exclusive PSA high-risk prostate cancer patients.

Prostate 2022 05 21;82(6):687-694. Epub 2022 Feb 21.

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

Background: The pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP).

Materials And Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (≥ pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP.

Results: Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p ≤ 0.001).

Conclusions: In cT1c-stage patients with high-risk PSA baseline, but low- to intermediate risk B-GGG, the rate of upgrading to GGG4 or GGG5 is low (11%). However, NOC stage is found in the majority (51%) and can be independently predicted with percentage of positive cores at biopsy and B-GGG.
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http://dx.doi.org/10.1002/pros.24313DOI Listing
May 2022

Effect of chemotherapy in metastatic prostate cancer according to race/ethnicity groups.

Prostate 2022 05 21;82(6):676-686. Epub 2022 Feb 21.

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

Background: No North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void.

Methods: We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014-2015). Separate and specific Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed.

Results: Of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63-0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54-1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73-1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11-0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group.

Conclusions: Caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities.
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http://dx.doi.org/10.1002/pros.24312DOI Listing
May 2022

Updating and Integrating Core Outcome Sets for Localised, Locally Advanced, Metastatic, and Nonmetastatic Castration-resistant Prostate Cancer: An Update from the PIONEER Consortium.

Eur Urol 2022 05 17;81(5):503-514. Epub 2022 Feb 17.

Academic Urology Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.

Context: Harmonisation of outcome reporting and definitions for clinical trials and routine patient records can enable health care systems to provide more efficient outcome-driven and patient-centred interventions. We report on the work of the PIONEER Consortium in this context for prostate cancer (PCa).

Objective: To update and integrate existing core outcome sets (COS) for PCa for the different stages of the disease, assess their applicability, and develop standardised definitions of prioritised outcomes.

Evidence Acquisition: We followed a four-stage process involving: (1) systematic reviews; (2) qualitative interviews; (3) expert group meetings to agree standardised terminologies; and (4) recommendations for the most appropriate definitions of clinician-reported outcomes.

Evidence Synthesis: Following four systematic reviews, a multinational interview study, and expert group consensus meetings, we defined the most clinically suitable definitions for (1) COS for localised and locally advanced PCa and (2) COS for metastatic and nonmetastatic castration-resistant PCa. No new outcomes were identified in our COS for localised and locally advanced PCa. For our COS for metastatic and nonmetastatic castration-resistant PCa, nine new core outcomes were identified.

Conclusions: These are the first COS for PCa for which the definitions of prioritised outcomes have been surveyed in a systematic, transparent, and replicable way. This is also the first time that outcome definitions across all prostate cancer COS have been agreed on by a multidisciplinary expert group and recommended for use in research and clinical practice. To limit heterogeneity across research, these COS should be recommended for future effectiveness trials, systematic reviews, guidelines and clinical practice of localised and metastatic PCa.

Patient Summary: Patient outcomes after treatment for prostate cancer (PCa) are difficult to compare because of variability. To allow better use of data from patients with PCa, the PIONEER Consortium has standardised and recommended outcomes (and their definitions) that should be collected as a minimum in all future studies.
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http://dx.doi.org/10.1016/j.eururo.2022.01.042DOI Listing
May 2022

Race/Ethnicity may be an Important Predictor of Life Expectancy in Localized Prostate Cancer Patients: Novel Analyses Using Social Security Administration Life Tables.

J Racial Ethn Health Disparities 2022 Feb 18. Epub 2022 Feb 18.

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

Purpose: To test the effect of race/ethnicity on Social Security Administration (SSA) life tables' life expectancy (LE) predictions in localized prostate cancer (PCa) patients treated with either radical prostatectomy (RP) or external beam radiotherapy (EBRT). We hypothesized that LE will be affected by race/ethnicity.

Patients And Methods: We relied on the 2004-2006 Surveillance, Epidemiology, and End Results database to identify D'Amico intermediate- and high-risk PCa patients treated with either RP or EBRT. SSA life tables were used to compute 10-year LE predictions and were compared to OS. Stratification was performed according to treatment type (RP/EBRT) and race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic/Latino, and Asian).

Results: Of 55,383 assessable patients, 40,490 were non-Hispanic White (RP 49.3% vs. EBRT 50.7%), 7194 non-Hispanic Black (RP 41.3% vs. EBRT 50.7%), 4716 Hispanic/Latino (RP 51.0% vs. EBRT 49.0%) and 2983 were Asian (RP 41.6% vs. EBRT 58.4%). In both RP and EBRT patients, OS exceeded life tables' LE predictions, except for non-Hispanic Blacks. However, in RP patients, the magnitude of the difference was greater than in EBRT. Moreover, in RP patients, OS of non-Hispanic Blacks virtually perfectly followed predicted LE. Conversely, in EBRT patients, the OS of non-Hispanic Black patients was worse than predicted LE.

Conclusions: When comparing SEER-derived observed OS with SSA life table-derived predicted life expectancy, we recorded a survival disadvantage in non-Hispanic Black RP and EBRT patients, which was not the case in the three other races/ethnicities (non-Hispanic Whites, Hispanic/Latinos, and Asians). This discrepancy should ideally be confirmed within different registries, countries, and tumor entities. Furthermore, the source of these discrepant survival outcomes should be investigated and addressed by health care politics.
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http://dx.doi.org/10.1007/s40615-022-01257-yDOI Listing
February 2022
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