Publications by authors named "Olivier Cussenot"

275 Publications

Marital status and prostate cancer incidence: a pooled analysis of 12 case-control studies from the PRACTICAL consortium.

Eur J Epidemiol 2021 Jul 18. Epub 2021 Jul 18.

Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, University of Quebec, 531 boul. des Prairies, Laval, QC, H7V 1B7, Canada.

While being in a committed relationship is associated with a better prostate cancer prognosis, little is known about how marital status relates to its incidence. Social support provided by marriage/relationship could promote a healthy lifestyle and an increased healthcare seeking behavior. We investigated the association between marital status and prostate cancer risk using data from the PRACTICAL Consortium. Pooled analyses were conducted combining 12 case-control studies based on histologically-confirmed incident prostate cancers and controls with information on marital status prior to diagnosis/interview. Marital status was categorized as married/partner, separated/divorced, single, or widowed. Tumours with Gleason scores ≥ 8 defined high-grade cancers, and low-grade otherwise. NCI-SEER's summary stages (local, regional, distant) indicated the extent of the cancer. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CI) for the association between marital status and prostate cancer risk, adjusting for potential confounders. Overall, 14,760 cases and 12,019 controls contributed to analyses. Compared to men who were married/with a partner, widowed men had an OR of 1.19 (95% CI 1.03-1.35) of prostate cancer, with little difference between low- and high-grade tumours. Risk estimates among widowers were 1.14 (95% CI 0.97-1.34) for local, 1.53 (95% CI 1.22-1.92) for regional, and 1.56 (95% CI 1.05-2.32) for distant stage tumours. Single men had elevated risks of high-grade cancers. Our findings highlight elevated risks of incident prostate cancer among widowers, more often characterized by tumours that had spread beyond the prostate at the time of diagnosis. Social support interventions and closer medical follow-up in this sub-population are warranted.
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http://dx.doi.org/10.1007/s10654-021-00781-1DOI Listing
July 2021

Standardizing immunohistochemistry methodology for evaluation of PD-1 and PDL-1 expression in upper tract urothelial carcinoma.

Can J Urol 2021 Jun;28(3):10719-10724

Sorbonne Université, GRC n∘5, Predictive Onco-Urology, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.

Introduction: Controversy regarding the prognostic and/or predictive role of PD-1 and PD-L1 expression for upper tract urothelial carcinoma (UTUC) could partly be explained by inconsistencies in the immunohistochemistry (IHC) methodology. Objective is to standardize the methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC patients.

Materials And Methods: Twenty-two cases treated with radical nephroureterectomy between 1996 and 2015 at 11 French hospitals were randomly selected to compare different methodologies for evaluation of PD-1 and PD-L1 expression. IHC was carried out on whole tissue sections and 0.6 mm- or 2 mm-core tissue micro-arrays (TMAs) using PD-1 NAT105 and PD-L1 28.8 or E1L3N on both tumor cells and tumor-infiltrating immune cells (TILs). Results obtained with whole tissue sections (WTS) were compared to those obtained with 0.6 mm- and 2 mm-core TMAs. Concordance was evaluated using Kappa coefficient.

Results: For evaluation of PD-1 and PD-L1 expression, the best concordance with WTS was observed using the PD-1 NAT105 and PD-L1 28.8 antibody on 2 mm-core TMAs, with 5% cut off for positivity on TILs and tumor cells, respectively (Kappa = 0.8).

Conclusions: The most accurate methodology for routine evaluation of PD-1 and PD-L1 expression in UTUC may be based on 2 mm-core TMAs using NAT105 and 28.8 antibodies with a 5% cut off for positivity on TILs and tumor cells, respectively.
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June 2021

Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24.

Prostate Cancer Prostatic Dis 2021 Jun 14. Epub 2021 Jun 14.

School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Background: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ.

Materials And Methods: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC.

Results: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings.

Conclusion: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.
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http://dx.doi.org/10.1038/s41391-021-00403-7DOI Listing
June 2021

"Virtually Perfect" for Some but Perhaps Not for All: Launching Telemedicine in the Bronx during the COVID-19 Pandemic. Letter.

J Urol 2021 07 27;206(1):176-177. Epub 2021 Mar 27.

Department of Urology and Clinical Research Group on Predictive Onco-Urology, APHP, Sorbonne University Paris, France.

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http://dx.doi.org/10.1097/JU.0000000000001773DOI Listing
July 2021

Restaging the Biochemical Recurrence of Prostate Cancer with [Ga]Ga-PSMA-11 PET/CT: Diagnostic Performance and Impact on Patient Disease Management.

Cancers (Basel) 2021 Mar 30;13(7). Epub 2021 Mar 30.

Department of Nuclear Medicine, Hôpital Tenon-AP-HP, Sorbonne Université, 75020 Paris, France.

Background: Detection rates of [Ga]Ga-PSMA-11 PET/CT on the restaging of prostate cancer (PCa) patients presenting with biochemical recurrence (BCR) have been well documented, but its performance and impact on patient management have not been evaluated as extensively.

Methods: Retrospective analysis of PCa patients presenting with BCR and referred for [Ga]Ga-PSMA-11 PET/CT. Pathological foci were classified according to six anatomical sites and evaluated with a three-point scale according to the uptake intensity. The impact of [Ga]Ga-PSMA-11 PET/CT was defined as any change in management that was triggered by [Ga]Ga-PSMA-11 PET/CT. The existence of a PCa lesion was established according to a composite standard of truth based on all clinical data available collected during the follow-up period.

Results: We included 294 patients. The detection rate was 69%. Per-patient sensitivity and specificity were both 70%. Patient disease management was changed in 68% of patients, and [Ga]Ga-PSMA-11 PET/CT impacted this change in 86% of patients. The treatment carried out on patient was considered effective in 89% of patients when guided by [Ga]Ga-PSMA-11 PET/CT versus 61% of patients when not guided by [Ga]Ga-PSMA-11 PET/CT ( < 0.001).

Conclusions: [Ga]Ga-PSMA-11 PET/CT demonstrated high performance in locating PCa recurrence sites and impacted therapeutic management in nearly two out of three patients.
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http://dx.doi.org/10.3390/cancers13071594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038030PMC
March 2021

Assessment of Xpert Bladder Cancer Monitor test performance for the detection of recurrence during non-muscle invasive bladder cancer follow-up.

World J Urol 2021 Mar 26. Epub 2021 Mar 26.

Sorbonne Université, GRC n°5, Predictive Onco-Urology, AP-HP, Hôpital Tenon, Service d'Urologie-Batiment Gabriel, 4 rue de la Chine, 75020, Paris, France.

Purpose: To assess the performance of the Xpert Bladder Cancer (BC) Monitor during the follow-up of patients with non-muscle invasive bladder cancer (NMIBC).

Methods: Patients with previously diagnosed NMIBC and followed up in clinical practice settings in two French urology departments between September 2017 and July 2019 were consecutively enrolled in this prospective observational study. Patients with a positive cystoscopy or computed tomography urogram underwent subsequent transurethral resection of the bladder, and/or biopsy, and the specimens were pathologically assessed. Cytology and Xpert BC Monitor tests were performed on urine samples. Xpert BC Monitor performance was assessed versus cystoscopy for disease-negative patients or versus histology for disease-positive patients, and was compared to that of cytology.

Results: Overall, 500 patients with a median age of 70.0 years were included. NMIBC recurrence was diagnosed in 44 cases (8.8%). Overall sensitivity, specificity, and negative predictive values (NPVs) were 72.7% (32/44), 73.7% (330/448) and 96.5% (330/342) for the Xpert BC Monitor, and 7.7% (2/26), 97.8% (310/317) and 92.8% (310/334) for cytology, respectively. The Xpert BC Monitor detected 92.3% (12/13) of the high-grade tumours and ruled out their presence in 99.7% (330/331) of cases. Analysis of the areas under the receiver operating characteristic curves demonstrated the superior performance of the Xpert BC Monitor over that of cytology.

Conclusion: Xpert BC Monitor performance was superior to that of cytology in the follow-up of NMIBC. The exclusion of aggressive tumours with a very high NPV (99.7%) supports the use of this urinary test in daily practice.
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http://dx.doi.org/10.1007/s00345-021-03629-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994915PMC
March 2021

Pathological reporting of cystectomy lymph nodes: a retrospective analysis of experience in Paris.

World J Urol 2021 Mar 20. Epub 2021 Mar 20.

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

Purpose: Pathological evaluation of pelvic lymph node (LN) dissection (PLND) is important for management of cystectomy patients. However, challenges such as unclear interobserver variability of LN counting remain. Here, we assess interobserver variability of LN measures and their clinical utility, with a focus on variant histology.

Methods: We retrieved radical cystectomy cases with PLND between 2010 and 2016 and reevaluated pathological parameters; number of total and metastatic LN, LN density (LND), length of metastatic LN and metastases, extranodal extension (ENE).

Results: We report 96 patients: median age of 71a, 34 cases pN+, 36 cases with any extent of variant histology, median follow-up 10 months. Perivesical LN were only rarely identified, but frequently metastatic (4/9). Variant histology (34 cases) frequently exhibited LN metastasis (53% of pN+ cases). Interobserver variance was poor for total LN (kappa = 0.167), excellent for positive LN (0.85) and pN staging (0.96), and mediocre for LND (0.53). ROC analysis suggests that both LND and the sum of LN metastasis length may predict outcome (AUC 0.83 and 0.75, respectively).

Conclusion: Our study confirms the notion of LND as a prognostic measure, but cautions due to strong interobserver variance of LN counts. The sum length of LN metastases could be a measure that is independent of LN counts. We find that microscopically identified perivesical LN merit particular attention. In summary, our study highlights current challenges in pathological reporting of PLND, confirms previous observations and forms a basis for further studies.
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http://dx.doi.org/10.1007/s00345-021-03630-8DOI Listing
March 2021

Limiting radiation exposure during prostatic arteries embolization: influence of patient characteristics, anatomical conditions, and technical factors.

Eur Radiol 2021 Mar 10. Epub 2021 Mar 10.

Department of Interventional Radiology and Oncology, Tenon Hospital, Sorbonne Université, 4 Rue de la Chine, 75020, Paris, France.

Objective: To assess the influence of patient characteristics, anatomical conditions, and technical factors on radiation exposure during prostatic arteries embolization (PAE) performed for benign prostatic hyperplasia.

Materials And Methods: Patient characteristics (age, body mass index (BMI)), anatomical conditions (number of prostatic arteries, anastomosis), and technical factors (use of cone beam computed tomography (CBCT), large display monitor (LDM), and magnification) were recorded as well as total air kerma (AK), dose area product (DAP), fluoroscopy time (FT), and number of acquisitions (NAcq). Associations between potential dose-influencing factors and AK using univariate analysis and a multiple linear regression model were assessed.

Results: Forty-one consecutive men (68 ± 8 years, min-max: 40-76) were included. LDM and CBCT decreased the use of small field of view with 13.9 and 3.8% respectively, both p < 0.001. The use of a LDM significantly reduced AK (1006.6 ± 471.7 vs. 1412 ± 754.6 mGy, p = 0.02), DAP (119.4 ± 64.4 vs. 167.9 ± 99.2, p = 0.04), FT (40.4 ± 11.5 vs. 53.6 ± 25.5 min, p = 0.01), and NAcq (16.3 ± 6.3 vs. 18.2 ± 7, p = 0.04). In multivariate analysis, AK reduction was associated with lower patient BMI (β = 0.359, p = 0.002), shorter FT (β = 0.664, p < 0.001) and CBCT use (β = - 0.223, p = 0.03), and decreased NAcq (β = 0.229, p = 0.04).

Conclusion: LDM and CBCT are important technical dose-related factors to help reduce radiation exposure during PAE, and should be considered in standard practice.

Key Points: • The use of large display monitor (LDM) and cone beam computed tomography (CBCT) both decreased the need for magnification during prostatic arteries embolization (PAE). • The use of LDM reduces radiation exposure during PAE. • Total air kerma is associated with patient's body mass index, fluoroscopy time, CBCT, and the number of acquisitions.
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http://dx.doi.org/10.1007/s00330-021-07844-7DOI Listing
March 2021

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Nat Commun 2021 02 23;12(1):1236. Epub 2021 Feb 23.

Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS (PHS, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10). Comparing the 80/20 PHS percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
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http://dx.doi.org/10.1038/s41467-021-21287-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902617PMC
February 2021

Bayesian predictive model to assess BRCA2 mutational status according to clinical history: Early onset, metastatic phenotype or family history of breast/ovary cancer.

Prostate 2021 May 18;81(6):318-325. Epub 2021 Feb 18.

GRC n°5 Predictive Onco-Urology, Tenon Hospital, AP-HP, Sorbonne University, Paris, France.

Background: Mutations of the BRCA2 gene are the most frequent alterations found in germline DNA from men with prostate cancer (PrCa), but clinical parameters that could better orientate for BRCA2 mutation screening need to be established.

Methods: Germline DNA from 325 PrCa patients (median age at diagnosis: 57 years old) was screened for BRCA2 mutation. The mutation frequency was compared between three subgroups: patients with an age at diagnosis at 55 years old and under (Group I); a personal or family history of breast, uterine or ovarian cancer (Group II); or a metastatic disease (Group III). Frequency of BRCA2 mutations was established for each combination of phenotypes, and compared between patients meeting or not the criteria for each subgroup using Fisher's exact test. Mutual information, direct effect, elasticity and contribution to the mutational status of each phenotype, taking into account overlap between subgroups, were also estimated using Bayesian algorithms.

Results: The proportion of BRCA2 mutation was 5.9% in Group I, 10.9% in Group II and 6.9% in Group III. The frequency of BRCA2 mutation was significantly higher among patients of Group II (p = .006), and reached 15.6% among patients of this group who presented a metastatic disease. Mutual information, direct effect, elasticity and contribution to the mutational status were the highest for phenotype II. Fifteen (71.4%) of the 21 BRCA2 mutation carriers had an aggressive form of the disease. Four (19%) of them died from PrCa after a median follow-up duration of 64.5 months.

Conclusions: Our results showed that a higher frequency of BRCA2 mutation carriers is observed, not only among PrCa patients with young onset or a metastatic disease, but also with a personal or a familial history of breast cancer.
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http://dx.doi.org/10.1002/pros.24109DOI Listing
May 2021

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing.

Eur J Cancer 2021 Mar 10;146:30-47. Epub 2021 Feb 10.

BRCA France Association, France. Electronic address:

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices.
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http://dx.doi.org/10.1016/j.ejca.2020.12.023DOI Listing
March 2021

Prognostic Impact of pT3 Subclassification in a Multicentre Cohort of Patients with Urothelial Carcinoma of the Renal Pelvicalyceal System Undergoing Radical Nephroureterectomy: A Propensity Score-weighted Analysis After Central Pathology Review.

Eur Urol Focus 2020 Oct 23. Epub 2020 Oct 23.

Sorbonne University, GRC 5 Predictive ONCO-URO, AP-HP, Urology, Pitie-Salpetriere Hospital, F-75013 PARIS, France. Electronic address:

Background: The current pathological tumour-node-metastasis (pTNM) classification for upper tract urothelial carcinoma (UTUC) does not include any risk stratification of pT3 renal pelvicalyceal tumours.

Objective: To assess the prognostic impact of pT3 subclassification in a multicentre cohort of patients with UTUC of the renal pelvicalyceal system undergoing radical nephroureterectomy (RNU).

Design, Setting, And Participants: Data from all consecutive patients treated with RNU for pT3 renal pelvicalyceal UTUC at 14 French centres from 1995 to 2013 were reviewed retrospectively.

Intervention: A central pathology review (CPR) was used to stratify pT3 patients into those with infiltration of the renal parenchyma on a microscopic level (pT3a) versus those with infiltration of the renal parenchyma visible on gross inspection of the resection specimen and/or invasion of peripelvic fat (pT3b).

Outcome Measurements And Statistical Analysis: Inverse probability weighting (IPW)-adjusted Cox regression analyses were used to compare recurrence-free survival (RFS) and cancer-specific survival (CSS) between pT3a and pT3b patients.

Results And Limitations: Overall, 202 patients were included and further stratified into pT3a (n = 98; 48.5%) and pT3b (n = 104; 51.5%) subgroups. Median time to follow-up in the weighted population was 68 (interquartile range, 50-95) mo. In IPW-adjusted Cox regression analyses, pT3b versus pT3a substage was associated with a significant adverse effect on RFS (hazard ratio [HR] = 2.02; 95% confidence interval [CI] = [1.36-3.01]; p < 0.001) and CSS (HR = 1.84; 95% CI = [1.20-2.82]; p = 0.005). The study is limited by its retrospective design.

Conclusions: Using IPW-adjusted analyses after the CPR, we observed that RNU patients with pT3b renal pelvicalyceal UTUC had adverse prognosis as compared with those with pT3a disease. As such, this subclassification could help refine the current pTNM system for UTUC.

Patient Summary: In this report, we looked at the prognostic interest of stratifying patients with pT3 renal pelvicalyceal upper tract urothelial carcinoma based on the extent of local invasion. We found that those with extensive infiltration (pT3b) had adverse prognosis as compared with those with limited infiltration (pT3a). This information could be provided on pathology reports to further guide clinical decision making.
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http://dx.doi.org/10.1016/j.euf.2020.10.004DOI Listing
October 2020

Homologous recombination deficiency (HRD) score in germline BRCA2- versus ATM-altered prostate cancer.

Mod Pathol 2021 Jun 18;34(6):1185-1193. Epub 2021 Jan 18.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The homologous recombination deficiency (HRD) score integrates three DNA-based measures of genomic instability, and has been understudied in prostate cancer. Given the recent FDA approval of two PARP inhibitors for prostate cancer, HRD score analysis could help to refine treatment selection. We assessed HRD score (defined as the sum of loss-of-heterozygosity, telomeric allelic imbalance, and large-scale state transitions) in three cohorts of primary prostate cancer, including a Johns Hopkins University (JHU) cohort with germline mutations in BRCA2, ATM, or CHEK2 (n = 64), the TCGA cohort (n = 391), and the PROGENE cohort (n = 102). In the JHU cohort, tumors with germline BRCA2 mutations had higher HRD scores (median = 27) than those with germline ATM or CHEK2 mutations (median = 16.5 [p = 0.029] and 9 [p < 0.001], respectively). For TCGA tumors without underlying HR pathway mutations, the median HRD score was 11, significantly lower than ovarian carcinoma lacking BRCA1/2 mutations (median = 28). In the absence of HR gene mutations, the median HRD score was unexpectedly higher among prostate cancers with TP53 mutations versus those without (17 vs. 11; p = 0.015); this finding was confirmed in the PROGENE cohort (24 vs. 16; p = 0.001). Finally, among eight BRCA2-altered patients who received olaparib, progression-free survival trended longer in those with HRD scores above versus below the median (14.9 vs. 9.9 months). We conclude that HRD scores are low in primary prostate cancer and higher in cases with germline BRCA2 or somatic TP53 mutations. Germline BRCA2-altered cases have significantly higher HRD scores than germline ATM-altered or CHEK2-altered cases, consistent with the lower efficacy of PARP inhibitors among the latter.
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http://dx.doi.org/10.1038/s41379-020-00731-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154637PMC
June 2021

Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study.

Eur Urol Oncol 2021 Jan 9. Epub 2021 Jan 9.

Institute of Biomedicine, University of Turku, Turku, Finland.

Background: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes.

Objective: To precisely estimate the contribution of germline ATM mutations to PrCa risk.

Design, Setting, And Participants: We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry.

Outcome Measurements And Statistical Analysis: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated.

Results And Limitations: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (<65 yr) had elevated tier 1 variant frequencies (p = 0.04). Tier 2 variants were also associated with PrCa risk, with an OR of 1.4 (95% CI: 1.1-1.7).

Conclusions: Carriers of pathogenic ATM variants have an elevated risk of developing PrCa and are at an increased risk for earlier-onset disease presentation. These results provide information for counselling of men and their families.

Patient Summary: In this study, we estimated that men who inherit a likely pathogenic mutation in the ATM gene had an approximately a fourfold risk of developing prostate cancer. In addition, they are likely to develop the disease earlier.
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http://dx.doi.org/10.1016/j.euo.2020.12.001DOI Listing
January 2021

Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.

Prostate Cancer Prostatic Dis 2021 Jun 8;24(2):532-541. Epub 2021 Jan 8.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.

Background: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).

Materials And Method: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.

Results: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.

Conclusions: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.
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http://dx.doi.org/10.1038/s41391-020-00311-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157993PMC
June 2021

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel.

Eur Urol 2021 Apr 6;79(4):480-488. Epub 2021 Jan 6.

Department of Urology, The Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK.

Background: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s.

Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression.

Design, Setting, And Participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel.

Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion.

Outcome Measurements And Statistical Analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves.

Results And Limitations: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review.

Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary.

Patient Summary: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.
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http://dx.doi.org/10.1016/j.eururo.2020.12.033DOI Listing
April 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

The Genetic Complexity of Prostate Cancer.

Genes (Basel) 2020 11 25;11(12). Epub 2020 Nov 25.

CeRePP/GRC5 Predictive Onco-Urology, Sorbonne University, 75020 Paris, France.

Prostate cancer (PCa) is a major concern in public health, with many genetically distinct subsets. Genomic alterations in PCa are extraordinarily complex, and both germline and somatic mutations are of great importance in the development of this tumor. The aim of this review is to provide an overview of genetic changes that can occur in the development of PCa and their role in potential therapeutic approaches. Various pathways and mechanisms proposed to play major roles in PCa are described in detail to provide an overview of current knowledge.
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http://dx.doi.org/10.3390/genes11121396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760266PMC
November 2020

Erratum to 'Prostate cancer local staging using biparametric MRI: Assessment and comparison with multiparametric MRI' [Eur. J. Radiol. 132 (2020) 109350].

Eur J Radiol 2020 Dec 20;133:109417. Epub 2020 Nov 20.

Academic Department of Radiology, Hȏpital Pitié-Salpétrière, Assistance Publique des Hȏpitaux de Paris, Paris, France; Academic Department of Radiology, Hȏpital Tenon, Assistance Publique des Hȏpitaux de Paris, Paris, France; Sorbonne Universités, GRC n◦ 5, Oncotype-Uro, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.ejrad.2020.109417DOI Listing
December 2020

The Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor.

Cancers (Basel) 2020 Nov 4;12(11). Epub 2020 Nov 4.

Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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http://dx.doi.org/10.3390/cancers12113254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694218PMC
November 2020

A four-antibody immunohistochemical panel can distinguish clinico-pathological clusters of urothelial carcinoma and reveals high concordance between primary tumor and lymph node metastases.

Virchows Arch 2021 Apr 30;478(4):637-645. Epub 2020 Oct 30.

Department of Pathology, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, 4 rue de la Chine, 75020, Paris, France.

Urothelial carcinoma of the bladder (UC) has a poor prognosis, partly because of chemotherapy resistance. Molecular classifications have shown their interest and can help to offer personalized treatment. In this study, we evaluated the feasibility of an immunohistochemical study to divide advanced UC into clinico-pathological-molecular subgroups and evaluate phenotypic correspondence between primary UC and matched lymph node metastases (LMN). An eight-antibody immunohistochemical panel was performed on UC and matched LMN from patients treated with radical cystectomy. One hundred eighty-seven UCs (100 pN0 tumor and 87 pN+ tumor) were tested. Multiple correspondence analysis showed that UC expressing GATA3 also expressed FOXA1 (p = 0.010) and did not stain for CK5/6 (p = 0.031) nor CK14 (p = 0.003). UC expressing CK14 coexpressed CK5/6 (p < 0.0001), had high Ki67 (p = 0.010) and no GATA3 (p = 0.003) nor FOXA1 (p = 0.011) expression. Loss of expression of STAG2 was associated with high Ki67 (p = 0.001). Sixty-seven percent of [CK5/6 CK14]+ [GATA3 FOAXA1]- patients had high Ki67 expression vs 37% of [GATA3 FOXA1]+ [CK5/6 CK14]- patients (p = 0.024). The majority of [CK5/6 CK14]+ [GATA3 FOAXA1]- patients (92%) had advanced disease (pT3-pT4) whilst 86% of pT1-T2 cases were [GATA3 FOXA1]+ [CK5/6 CK14]- (p = 0.041). Differential antigen expression between 63 pN+ primary tumors and their corresponding LNM showed the following concordance percentages: p53 (76%), p63 (75%), CK5/6 (65%), CK14 (89%), GATA3 (75%), FOXA1 (68%), STAG2 (65%), and Ki-67 (71%). These results support the interest of immunohistochemistry for subtype profiling in metastatic UC, using CK5/6, CK14, GATA3, and FOXA1, highlighting also few phenotypical modifications when tumor spreads to lymph nodes.
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http://dx.doi.org/10.1007/s00428-020-02951-0DOI Listing
April 2021

Diagnosis of prostate cancer in one day: The benefits of cytology in tumour detection.

Cytopathology 2021 Mar 22;32(2):211-216. Epub 2020 Dec 22.

GRC5 predictive onco-urology, Sorbonne University, Paris, France.

Objective: Prostate cancer (PCa) is a frequent and mortal disease. The aim of this study was to introduce a "diagnosis and handling of PCa in one day" concept, accelerating the handling of PCa patients by giving diagnostic results within 3 hours with the help of prostate cytology. Standard histology served as the control.

Material And Methods: After multiparametric MRI, prostate biopsies were taken and one was used for imprint cytology on superfrost slides. The cytology samples were stained by p63/p504s double staining, a standard stain in PCa histology, followed by on-site interpretation.

Results: Among 129 patients, 39.5% had a prior history of PCa and were either under active surveillance or had been treated by focal therapy. The others came with suspicion of PCa. In 80.8% of the cases, the cytology and histology results agreed. In low-grade PCa the detection with cytology was more difficult with 72.4% agreement, whereas for intermediate and high-grade PCa the concordance with histology was 81.8 and 90%, respectively. False positive cases were less than 4.0%.

Conclusion: Cytology of the prostate is unusual, but our study is the first to show it is feasible and gives immediate results that are satisfactory, especially in more aggressive cases. Immunocytology can be easily integrated into the laboratory. Our technique allows quicker handling of PCa, which can soften the psychological impact on men waiting for the diagnosis of PCa.
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http://dx.doi.org/10.1111/cyt.12930DOI Listing
March 2021

Prostate cancer local staging using biparametric MRI: assessment and comparison with multiparametric MRI.

Eur J Radiol 2020 Nov 15;132:109350. Epub 2020 Oct 15.

Academic Department of Radiology, Hôpital Pitié-Salpétrière, Assistance Publique des Hôpitaux de Paris, Paris, France; Academic Department of Radiology, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Paris, France; Sorbonne Universités, GRC n° 5, Oncotype-Uro, Paris, France. Electronic address:

Purpose: The value of adding dynamic contrast-enhanced (DCE) imaging to T2-weighted (T2W) magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) to improve the detection and staging of prostate cancer (PCa) is unclear. The aim of this retrospective study was to compare the diagnostic performance of non-contrast biparametric MRI (bpMRI) with multiparametric MRI (mpMRI), for local staging of PCa.

Methods: Ninety-two patients who underwent prostate MRI on a 3-Tesla MRI system before radical prostatectomy for PCa were included retrospectively. Four readers independently assigned a Likert score (ranging from 1 to 5) for predicting extra-prostatic extension (EPE) on T2W + DWI (bpMRI) and then on T2W + DWI + DCE imaging (mpMRI). MRI-based staging results were compared with radical prostatectomy histology. A prediction of EPE generalized linear mixed model was used to assess the added-value of DCE and discriminative power of staging accuracy by area under the receiver-operating curve (AUC ROC).

Results: AUC was not significantly improved by DCE (mpMRI, AUC = 0.73 [95%CI: 0.655‒0.827] vs. bpMRI, AUC = 0.76 [95%CI: 0.681‒0.846]). After applying a selection procedure, only MRI criteria were retained in a multivariate model. The following criteria were significantly associated with local extension: localization in the peripheral zone (p < 0.001), maximal diameter of the lesion (<0.0001), curvilinear capsular contact on T2W (p < 0.0001), capsular irregularity on T2W (p < 0.0001), bulging on T2W (p < 0.001) and seminal vesicle hypo-signal (p < 0.001).

Conclusion: Use of bpMRI did not result in a decrease in local staging accuracy.
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http://dx.doi.org/10.1016/j.ejrad.2020.109350DOI Listing
November 2020

Postoperative assessment of nosocomial transmission of COVID-19 after robotic surgical procedures during the pandemic.

Urol Oncol 2021 05 21;39(5):298.e7-298.e11. Epub 2020 Sep 21.

Sorbonne University, GRC n 5, Predictive Onco-Urology, APHP, Hôpital Pitié-Salpêtrière, Urology, Paris, France. Electronic address:

Objectives: To assess potential nosocomial coronavirus disease-2019 (COVID-19) transmission in patients who underwent robot-assisted laparoscopic procedures during the pandemic.

Material And Methods: Prospective study in patients undergoing robot-assisted laparoscopy in urology or gynaecology within 2 academic hospitals. Patients underwent local preoperative COVID-19 screening using a symptoms questionnaire. Patients with suspicious screening underwent coronavirus real time-polymerase chain reaction (RT-PCR) and were excluded from robotic surgery if positive. Patients with symptoms postsurgery were systematically tested for coronavirus by RT-PCR. One-month postsurgery, all patients had a telephone consultation to evaluate COVID-19 symptoms.

Results: Sixty-eight patients underwent robotic surgery during the study period (median age: 63-years [IQR: 53-70], 1.8 male: female ratio). Oncology was the main indication for robotic surgery (n = 62, 91.2%) and 26 patients (38.2%) received a chest CT-scan prior to surgery. Eleven patients (16.2%) were symptomatic after surgery of whom only 1 tested positive for coronavirus by RT-PCR (1.5%) and was transferred to COVID-19 unit with no life-threatening condition. No attending surgeon was diagnosed with COVID-19 during the study.

Conclusions: Robot-assisted laparoscopic surgery seemed safe in the era of COVID-19 as long as all recommended precautions are followed. The rate of nosocomial COVID-19 transmission was extremely low despite the fact that we only used RT-PCR testing in symptomatic patients during the preoperative work-up. Larger cohort is needed to validate these results.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505595PMC
May 2021

Genetic variability in 13q33 and 9q34 is linked to aggressiveness patterns and a higher risk of progression of non-muscle-invasive bladder cancer at the time of diagnosis.

BJU Int 2021 Mar 15;127(3):375-383. Epub 2020 Oct 15.

GRC n°5 Predictive Onco-Urology, AP-HP, Tenon Hospital, Sorbonne University, Paris, France.

Objective: To identify single nucleotide polymorphisms (SNPs) associated with patterns of aggressiveness of non-muscle-invasive bladder cancer (NMIBC).

Patients And Methods: From January 2011 to December 2018, 476 patients with NMIBC were prospectively included. The first step aimed to identify SNPs associated with aggressiveness patterns (e.g. ≥pT1or high-grade/Grade 3 or presence of carcinoma in situ) by analysing the data of a genome-wide association study (GWAS) on 165 patients with BC. The second step aimed to validate the SNPs previously identified, by genotyping the germline DNA of 311 patients with NMIBC.

Results: Overall, the median (interquartile range) age was 66 (58-75) years and the rate of patients with aggressive NMIBC was comparable between both groups (46% vs 46%, P = 1). GWAS data analysis identified four SNPs associated with an aggressive NMIBC (rs12615669, rs4976845, rs2989734, and rs2802288). In the validation cohort, the genotype CC of rs12615669, as well as age >70 years at the time of diagnosis were associated with aggressive NMIBC (P = 0.008 and P < 0.001, respectively). Genotyping of the entire cohort showed an association between aggressive NMIBC and the T allele of rs12615669 (P = 0.0007), the A allele of rs4976845 (P = 0.012), and the A allele of rs2989734 (P = 0.007). A significant association was also found for the entire cohort between the risk of progression and the A allele of rs4976845 (P = 0.04).

Conclusion: This two-phase study identified three SNPs (rs12615669, rs4976845, and rs2989734) associated with aggressive NMIBC and one SNP (rs4976845) associated with a higher risk of progression.
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http://dx.doi.org/10.1111/bju.15254DOI Listing
March 2021

African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer.

Int J Cancer 2021 01 24;148(1):99-105. Epub 2020 Sep 24.

UMR Inserm 1134 Biologie Intégrée du Globule Rouge, INSERM/Université Paris Diderot-Université Sorbonne Paris Cité/INTS/Université des Antilles, Paris, France.

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.
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http://dx.doi.org/10.1002/ijc.33282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135907PMC
January 2021

Circadian genes polymorphisms, night work and prostate cancer risk: Findings from the EPICAP study.

Int J Cancer 2020 12 20;147(11):3119-3129. Epub 2020 Jul 20.

Université Paris-Saclay, UVSQ, Inserm, CESP, Villejuif, France.

Over the past two decades, several studies have attempted to understand the hypothesis that disrupting the circadian rhythm may promote the development of cancer. Some have suggested that night work and some circadian genes polymorphisms are associated with cancer, including prostate cancer. Our study aims to test the hypothesis that prostate cancer risk among night workers may be modulated by genetic polymorphisms in the circadian pathway genes based on data from the EPICAP study, a population-based case-control study including 1511 men (732 cases/779 controls) with genotyped data. We estimated odds ratio (ORs) and P values of the association between prostate cancer and circadian gene variants using logistic regression models. We tested the interaction between circadian genes variants and night work indicators that were significantly associated with prostate cancer at pathway, gene and SNP levels. Analyses were also stratified by each of these night work indicators and by cancer aggressiveness. The circadian pathway was significantly associated with aggressive prostate cancer among night workers (P = .004), particularly for men who worked at night for <20 years (P = .0002) and those who performed long night shift (>10 hours, P = .001). At the gene level, we observed among night workers significant associations between aggressive prostate cancer and ARNTL, NPAS2 and RORA. At the SNP-level, no significant association was observed. Our findings provide some clues of a potential modulating effect of circadian genes in the relationship between night work and prostate cancer. Further investigation is warranted to confirm these findings and to better elucidate the biological pathways involved.
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http://dx.doi.org/10.1002/ijc.33139DOI Listing
December 2020

Transurethral resection of bladder and radical cystectomy: Concordance of histology. Are we good enough?

Turk J Urol 2020 Sep 1;46(5):354-359. Epub 2020 Jun 1.

Department of Pathology, Tenon Hospital, APHP, Sorbonne University, Paris, France.

Objective: Urothelial carcinoma (UC) is heterogeneous, and variant histologies (VH) are more frequent than initially reported. Reporting VH is recommended by several guidelines because of prognostic and therapeutic implications. We evaluated the concordance of VH between the first transurethral resections of the bladder (TURBs) and the following radical cystectomy (RC). This paper is the first to compare VH with a central pathology review between TURB and RC.

Material And Methods: In this retrospective study, we only included those patients who underwent TURB with VH and then RC between 01/2010 and 12/2013 at our institution. The presence of VH in both TURB and RC was assessed and compared according to the 2016 World Health Organization (WHO) classification by a central pathology review.

Results: Among 110 patients who had the initial TURB/RC, 54 (49.1%) were diagnosed with VH, 48 (43%) had a single pattern, and six had (5%) multiple histological patterns. Squamous differentiation was the most common single VH (31%). Twenty patients with UC (18%) showed discordance between TURB and RC, especially in micropapillary versus nested (n=3) cases. Concordant histology between TURB/RC was seen in 82% of the cases.

Conclusion: Discrepancies can be seen between TURB and RC when reporting VH, which can be problematic for selection of therapy and management. TURB alone might be insufficient to evaluate the presence of VH, especially in VH with heavy therapeutic implications, such as micropapillary carcinomas. Nevertheless, concordance with a central review by an experienced uropathologist when applying the WHO 2016 classification is 82%.
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http://dx.doi.org/10.5152/tud.2020.20121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483458PMC
September 2020