Overall and metastasis-free survival of Afro-Caribbean patients with biochemical recurrence after radical prostatectomy.

INTRODUCTION: Early salvage radiotherapy is indicated for patients with biochemical recurrence after radical prostatectomy. However, for various reasons, certain patients do not benefit from this treatment (OBS) or only at a late stage (LSR). There are few studies on this subject and none on a "high-risk" population, such as patients of African descent. Our objective was to estimate the metastasis-free (MFS) and overall survival (OS) of patients who did not receive salvage radiotherapy, and to identify risk factors of disease progression. PATIENTS AND METHODS: This was a single-center retrospective study that included 154 patients, 99 in the OBS group and 55 in the LSR group. All were treated by total prostatectomy for localized prostate cancer between January 2000 and December 2020 and none received early salvage radiotherapy after biochemical recurrence. RESULTS: Baseline characteristics were similar between groups, except for the time to biochemical recurrence. The median follow-up was 10.0 and 11.8 years for the OBS and LSR groups, respectively. The median time from surgery to LSR was 5.1 years. The two groups did not show a significant difference in MFS: 90.6% at 10 years for the OBS group and 93.3% for the LSR group. The median MFS was 19.8 and 19.6 years for the OBS and LSR groups respectively. OS for the OBS group was significantly higher than that for the LSR group (HR: 2.14 [1.07-4.29]; p = 0.03), with 10-year OS of 95.9% for the OBS group and 76.1% for the LSR group. Median OS was 16 and 15.6 years for the OBS and LSR groups, respectively. CONCLUSION: In this study, we observed satisfactory metastasis-free and OS rates relative to those reported in the scientific literature. The challenge is not to question the benefit of early salvage radiotherapy, but to improve the identification of patients at risk of progression through the development of molecular and genomic tests for more highly personalized medicine.

Asymptomatic Bacteriuria and Urological Surgery: Risk Factor or Not? Results From the National and Multicenter TOCUS Database.

PURPOSE: Current guidelines recommend screening and treatment of asymptomatic bacteriuria prior to all urological surgeries breaching the mucosa. But little evidence supports this recommendation. At the least, risk stratification for postoperative UTI to support this strategy is lacking. The aim of this study was to define the associated factors for postoperative febrile infectious complications (UTI or surgical site infection) in urological surgery. MATERIALS AND METHODS: We conducted a retrospective, multicentric study including all consecutive patients undergoing any urological surgery with preoperative urine culture. The primary outcome was the occurrence of a UTI or surgical site infection occurring within 30 days after surgery. RESULTS: From 2016 to 2023, in 10 centers, 2389 patients were included with 838 (35%) positive urine cultures (mono-/bi-/polymicrobial). Postoperative infections occurred in 106 cases (4.4%), of which 44 had negative urine cultures (41%), 42 had positive mono-/bimicrobial urine cultures (40%), and 20 had polymicrobial urine cultures (19%). In multivariable analysis, UTI during the previous 12 months of surgery (odds ratio [OR] 3.43; 95% CI 2.07-5.66; P < .001), monomicrobial/bimicrobial preoperative urine culture (OR 3.68; 95% CI 1.57-8.42; P = .02), polymicrobial preoperative urine culture (OR 2.85; 95% CI 1.52-5.14; P < .001), and operative time (OR 1.09; 95% CI 1.04-1.15; P < .001) were independent associated factors for postoperative febrile infections. CONCLUSIONS: Positive urine culture, including preoperative polymicrobial urine culture, prior to urological surgery was associated with postoperative infection. Additionally, patients experiencing infectious complications also had a higher incidence of other complications. The effectiveness of systematic preventive antibiotic therapy for a positive urine culture has not been conclusively established.

Asymptomatic bacteriuria prior to partial and radical nephrectomy: To screen or not to screen? Results from the national and multicenter TOCUS database.

INTRODUCTION: In the era of increased bacterial resistance, the main strategy is to reduce the prescription of antibiotics when possible. Nowadays, it is highly recommended to screen for asymptomatic bacteriuria (ABU), prior to urological surgery with potential mucosal breach or urine exposure. Screening and treating urinary colonization is a strategy widely adopted before radical and partial nephrectomy but without any evidence. Our main end point in this study is to analyze the relationship between preoperative urine culture and the risk of postoperative febrile urinary tract infection (UTI) or surgical-site infection (SSI) in partial or radical nephrectomy patients. METHODS: We conducted a multicenter retrospective cohort study between January 2016 and January 2023 in 11 French tertiary referral hospitals (TOCUS database). We collected the data for 269 patients including several pre-, intra-, and post-operative variables that could potentially increase the risk of postoperative UTI and SSI including preoperative urinary culture results. RESULTS: The incidence rate of postoperative UTI and SSI was 8.9% in our study. After conducting a logistic multivariate analysis, a propensity score matching analysis, and a subgroup analysis, we found no significant correlation between the urine culture and the postoperative UTI risk [OR = 1.2 (0.5-2.7) (p = 0.7)]. Only the postoperative non-infectious complications were related to a higher risk of postoperative UTI [OR = 12 (4-37), p < 0.001)]. CONCLUSION: Our research shows that screening and treating for ABU prior to radical or partial nephrectomy seems to be unnecessary to prevent postoperative UTI and SSI.

Effectiveness of a digital telemonitoring platform for cancer care of older patients: The ConnectElderlyPatientToDoctor study.

While telemedicine has been shown to improve the quality of care for cancer patients, it remains underused for older patients (OP), partly due to the assumption that OPs are unabled or unwilling to use digital tools. However, more than 50% of new cancers are diagnosed in people over 70. The ConnectElderlyPatientToDoctor study aimed to evaluate the OP compliance with the use of the digital telemonitoring platform Cureety in oncology. All cancer patients followed at the Military Hospital Bégin were eligible for the study. Patients were invited to respond to a symptomatology questionnaire personalized to their pathology and treatment. An algorithm evaluated the health status of the patient based on the reported adverse events. The population was divided into two groups, OP and younger patients (YP), based on a cut-off at 70 years. The primary endpoint was to assess the compliance of OPs with the use of the digital oncology platform Cureety, compared to YP. From July 2020 to September 2021, a total of 117 patients were included in our study. We found that 66% of the patients were compliant, with no difference between the two groups (71.2% of YP, 61.7% of OP, P = .29). In OPs, progression free survival (PFS) ratio at 6-months was 64.6% in the tolerant patients vs 23.4% in the nontolerant patients (HR = 0.1980, 95% CI = 0.04431-0.8845, P = .0339). The median PFS was 23.3 months in the tolerant group vs 3.3 months in the nontolerant group (P = .0339). The data of overall survival are immature. OPs had a clear benefit from using this platform, similar to what was observed for YP. Patients felt less isolated and felt that they benefited from personalized care with early ambulatory medical care of adverse events. We also found that the health indicators collected with the platform in the first month of treatment are predictive of the progression of the disease. This solution makes it possible to streamline and improve the care pathway of OP.

Micro-ultrasound-guided biopsies versus systematic biopsies in the detection of prostate cancer: a systematic review and meta-analysis.

PURPOSE: The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet. METHODS: We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB. RESULTS: Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56-71% of men, with 31.3-49% having csPCa and 17-25.4% having non-csPCa. Regarding csPCa, mUS-guided biopsies identified 196 and SB 169 cases (Detection Ratio (DR): 1.18, 95% CI 0.83-1.68, I2 = 69%), favoring mUS-guided biopsies; regarding non-csPCa, mUS-guided biopsies identified 62 and SB 115 cases (DR: 0.55, 95% CI 0.41-0.73, I2 = 0%), also favoring mUS-guided biopsies by decreasing unnecessary diagnosis. CONCLUSION: Micro-ultrasound-guided biopsies compared favorably with SB for the detection of csPCa and detected fewer non-csPCa than SB. Prospective trials are awaited to confirm the interest of adding mUS-guided biopsies to MRI-TB to optimize csPCa detection without increasing overdiagnosis of non-csPCa.

What is the ideal combination therapy in de novo, oligometastatic, castration-sensitive prostate cancer?

PURPOSE: To review current evidence regarding the management of de novo, oligometastatic, castration-sensitive prostate cancer (PCa). METHODS: A literature search was conducted on PubMed/Medline and a narrative synthesis of the evidence was performed in August 2022. RESULTS: Oligometastatic disease is an intermediate state between localized and aggressive metastatic PCa defined by ≤ 3-5 metastatic lesions, although this definition remains controversial. Conventional imaging has limited accuracy in detecting metastatic lesions, and the implementation of molecular imaging could pave the way for a more personalized treatment strategy. However, oncological data supporting this strategy are needed. Radiotherapy to the primary tumor should be considered standard treatment for oligometastatic PCa (omPCa). However, it remains to be seen whether local therapy still has an additional survival benefit in patients with de novo omPCa when treated with the most modern systemic therapy combinations. There is insufficient evidence to recommend cytoreductive radical prostatectomy as local therapy; or stereotactic body radiotherapy as metastasis-directed therapy in patients with omPCa. Current data support the use of intensified systemic therapy with androgen deprivation therapy (ADT) and next-generation hormone therapies (NHT) for patients with de novo omPCa. Docetaxel has not demonstrated benefit in low volume disease. There are insufficient data to support the use of triple therapy (i.e., ADT + NHT + Docetaxel) in low volume disease. CONCLUSION: The present review discusses current data in de novo, omPCa regarding its definition, the increasing role of molecular imaging, the place of local and metastasis-directed therapies, and the intensification of systemic therapies.

Metabolic syndrome and prostate cancer in Afro-Caribbean men.

INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a group of risk factors that increases the likelihood of developing cardiovascular diseases. Although suggested, the relationship between MetS and prostate cancer (PCa) is still inconclusive. Very few studies have addressed this question in populations of African descent, which are disproportionately affected by PCa. This study aimed to assess the prevalence of MetS among incident cases of Afro-Caribbean PCa and estimate its association with adverse clinicopathological features and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: We included 285 consecutive patients with incident cases of PCa attending the University Hospital of Guadeloupe (French West Indies). MetS was evaluated at the time of diagnosis by collecting information on blood pressure, glycaemic status, triglyceride and high-density lipoprotein cholesterol levels, and obesity through various surrogates, including two waist circumference indicators (≤94 cm, ≥102 cm), the waist-to-hip ratio (≥0.95), and body mass index (BMI; ≥30 kg/m2 ). We followed 245 patients who underwent RP as primary treatment of localized PCa. RESULTS: The prevalence of MetS varied greatly, from 31.6% to 16.4%, when a waist circumference ≥94 cm or BMI were used as obesity surrogates, respectively. No significant associations were found between MetS, regardless of the obesity criteria employed, and the risk of adverse pathological features or BCR. CONCLUSIONS: The high variability in MetS resulting from the diversity of obesity criteria used may explain the discordant associations reported in the literature. Further studies using strict and uniform criteria to define MetS on homogeneous ethnic groups are encouraged to clarify the association, if any, between MetS and PCa outcomes.

Overall and progression-free survival of Afro-Caribbean men with metastatic castration-resistant prostate cancer (mCRPC).

INTRODUCTION: Several studies in the Caucasian population have shown the benefit of using docetaxel, abiraterone, or enzalutamide for patients with metastatic prostate cancer at the castration-resistant stage (mCRPC). However, there are no strong data for men of African ancestry. The objective of this study was to estimate the overall and progression-free survival of patients according to these treatments at the mCRPC stage. PATIENTS AND METHODS: This was a monocentric retrospective study that consecutively included 211 men with mCRPC between June 1, 2009 and August 31, 2020. The primary end point was overall survival (OS). The secondary end point was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed. RESULTS: The present study included 180 patients for analyses. There was no difference in OS (log-rank test = 0.73), with a median follow-up of 20.7 months, regardless of the treatment administered in the first line. Men with mCRPC who received hormonotherapy (abiraterone or enzalutamide) showed better progression-free survival than those who received docetaxel (log-rank test = 0.004), with a particular interest for abiraterone hazard ratio (HR) = 0.51 (95% confidence interval: 0.39-0.67). The patient characteristics were similar, except for bone lesions, irrespective of the treatment administered in the first line. After univariate then multivariate analysis, only World Health Organization status and metastases at diagnosis were significantly associated with progression. CONCLUSION: Our results suggest the use of hormonotherapy (abiraterone or enzalutamide) with a tendency for abiraterone in first line for men with African ancestry at the mCRPC stage.

DNA damage repair gene germline profiling for metastatic prostate cancer patients of different ancestries.

BACKGROUND: Germline and somatic mutations in DNA damage repair genes (DDRg) are now recognized as new biomarkers for the management of metastatic prostate cancers (mPC). We evaluate the frequency of germline DDRg mutations among French mPC patients of European and African ancestries. METHODS: Targeted next-generation sequencing of 21 DDRg was performed on germline DNA from 557 mPC patients, including 15.1% of cases with an African origin. RESULTS: Forty-seven germline mutations in 11 DDR genes were identified in 46 patients of the total cohort (8.3%). BRCA2 (4.1%) and ATM (2.0%) were the most frequently mutated genes. There was no difference in DDRg mutation frequency between mPC patients of European ancestry and those of African origin. Germline mutations of BRCA2 were associated with a positive family history of breast cancer (p = 0.02). The mean age at metastatic stage (59.7 vs. 67.0; p = 0.0003) and the mean age at death (65.2 vs. 73.9; p = 0.0003) were significantly earlier for carriers of BRCA2 mutation than for non-carriers. Moreover, the Cox model showed that BRCA2 positive status was statistically associated with poorer survival (hazard ratio: 0.29; 95% confidence interval 0.18-0.48; p < 0.0001). CONCLUSION: We showed that, in France, BRCA2 and ATM are the main predisposing DDR genes in mPC patients, with a particular aggressiveness for BRCA2 leading to early metastatic stage and death.

Heterogeneity of contemporary grade group 4 prostate cancer in radical prostatectomy specimens.

PURPOSE: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. METHODS: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. RESULTS: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. CONCLUSIONS: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.

Annual nationwide analysis of costs and post-operative outcomes after radical prostatectomy according to the surgical approach (open, laparoscopic, and robotic).

OBJECTIVE: Annual countrywide data are scarce when comparing surgical approaches in terms of hospital stay outcomes and costs for radical prostatectomy (RP). We aimed to assess the impact of surgical approach on post-operative outcomes and costs after RP by comparing open (ORP), laparoscopic (LRP), and robot-assisted (RARP) RP in the French healthcare system. PATIENTS AND METHODS: Data from all patients undergoing RP in France in 2020 were extracted from the central database of the national healthcare system. Primary endpoints were length of hospital stay (LOS including intensive care unit (ICU) stay if present), complications (estimated by severity index), hospital readmission rates (at 30 and 90 days), and direct costs of initial stay. RESULTS AND LIMITATIONS: A total of 19,018 RPs were performed consisting in ORP in 21.1%, LRP in 27.6%, and RARP in 51.3% of cases. RARP was associated with higher center volume (p < 0.001), lower complication rates (p < 0.001), shorter LOS (p < 0.001), and lower readmission rates (p = 0.004). RARP was associated with reduced direct stay costs (2286 euros) compared with ORP (4298 euros) and LRP (3101 euros). The main cost driver was length of stay. The main limitations were the lack of mid-term data, readmission details, and cost variations due to surgery system. CONCLUSIONS: This nationwide analysis demonstrates the benefits of RARP in terms of post-operative short-term outcomes. Higher costs related to the robotic system appear to be balanced by patient care improvements and reduced direct costs due to shorter LOS.

Therapeutic failures of targeted antibiotic prophylaxis in urology.

Targeted antibiotic prophylaxis (TAP) is required for patients with positive urine culture before urological surgery. Our aim was to determine the efficacy of TAP. This was a prospective single-center study performed in a urology department. All patients who underwent a programmed surgery were included. Urine culture was obtained before surgery requiring a prophylaxis: in the case of sterile urines, antibiotics were used in accordance with national recommendations; for positive urine culture, a TAP was used in accordance with susceptibility testing. The drugs were administered for 2 days before surgery until withdrawal of bladder catheter. The occurrence of healthcare-associated infections was registered until day 30 after surgery. Two hundred three patients were included for 8 non-consecutive weeks in 2020, among whom fifteen were lost of sight before day 30. Among the remaining 188 patients, most frequent surgeries were 75 prostatic diseases (40%), 50 endo-ureteral surgeries for JJ stent insertion (27%), and 23 bladder cancers (12%). One hundred forty-eight (79%) patients required a urine culture before procedure; 142/148 (96%) urine cultures were performed, leading to 74 TAP. The main isolated bacteria were 48 Enterobacteriaceae and 8 Enterococcus spp. TAP was cotrimoxazole (n = 30), aminoglycosides (n = 11), amoxicillin (n = 9), fluoroquinolones (n = 7), and others (n = 17). The rate of healthcare-associated infections was 14.8% (11/74), including six microbiologically documented antibiotic failures. The rate of healthcare-associated infection after urological surgery using TAP was high, implying to discuss the choice and the dosage of the antibiotic molecules.

Use of Antibiotic Prophylaxis for Polymicrobial Urine Culture before Urological Surgery: A Pilot Study.

INTRODUCTION: Preoperative polymicrobial urine cultures are common, but the associated risk of nosocomial infection is currently unknown. We aimed to analyze the risk of postoperative infection in patients with preoperative polymicrobial urine cultures. METHODS: This was a prospective cohort study conducted from November 2018 to October 2020. Polymicrobial urine cultures were defined by at least the presence of 3 bacteria without leukocyturia threshold on two consecutive samples in the month preceding the surgical procedure. Data on postoperative infections were collected during hospitalization until day 30. A postoperative infection was defined by the occurrence of clinical signs (fever, chills, and suppurated process on the surgical site) associated with the prescription of an antibiotic therapy. RESULTS: Sixty-eight patients were included, and seven developed a postoperative infection with a microbe identified in blood or urine cultures. There was a significant association between leukocyturia ≥104 (p = 0.02) and the administration of intraoperative antibiotic prophylaxis (p < 0.001). In contrast, there was no significant association between postoperative infections for patients with polymicrobial preoperative urine cultures and having received or not an empirical antibiotic therapy. CONCLUSION: The rate of postoperative infection in patients with polymicrobial urine culture before urological procedure was 10.2%. Further studies are needed to assess the antibiotic prophylaxis to be used in this situation.

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

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.

Characteristics and progression-free survival of Afro-Caribbean men with metastatic hormone-sensitive prostate cancer at the time of diagnosis.

INTRODUCTION AND OBJECTIVES: Metastatic hormone-sensitive prostate cancer (mHSPC) accounts for 12% of prostate cancers diagnosed in Guadeloupe according to the Guadeloupean cancer registry. Most published studies have been conducted on the Caucasian population, whereas data concerning mHSPC in the Afro-Caribbean population are lacking. We aimed to describe the patient characteristics and estimate the progression-free survival of men with mHSPC in an Afro-Caribbean population according to the available treatment. PATIENTS AND METHODS: This was a monocentric retrospective study that consecutively included 133 men with mHSPC between January 1, 2015 and December 31, 2019 at the University Hospital of Guadeloupe. The primary endpoint was a description of the patients' characteristics with a description of complications at diagnosis. The secondary endpoint was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed. RESULTS: The median age at diagnosis was 71 years. The median prostate-specific antigen (PSA) was 147 ng/ml and 37% of patients presented with a disease-related complication at diagnosis. The survival analysis according to treatment showed median survival of 15 months for the androgen deprivation therapy (ADT) + chemotherapy group, 20 months for the ADT + new hormone therapy group, and 21.5 months for the ADT alone group, with no significant difference between the three therapeutic options (log-rank test: 0.27). In univariate analysis, none of the patient characteristics at diagnosis (i.e., age, PSA, bone lesions, visceral lesions) were significantly associated with the risk of progression, regardless of the treatment. CONCLUSION: There was no significant difference in terms of progression-free survival between currently validated treatments administered in the first line, regardless of the tumor volume or risk group. Future studies with larger numbers of patients and involving molecular factors are required to confirm or invalidate these results and understand the evolution of prostate cancer in our population and thus better prevent complications related to the disease.

Tissue cholesterol metabolism and prostate cancer aggressiveness: Ethno-geographic variations.

BACKGROUND: Prostate cancer (PCa) is more frequent and more aggressive in populations of African descent than in Caucasians. Since the fatty acid composition of peri-prostatic adipose tissue (PPAT) has been shown to differ according to the ethno-geographic origin and is involved in PCa aggressiveness, we aimed to analyze the cholesterol content of PPAT from Caucasian and African-Caribbean patients, in correlation with markers of disease aggressiveness and cholesterol metabolism in cancer tissues. METHODS: The quantification of cholesterol in PPAT was analyzed in 52 Caucasian and 52 African-Caribbean PCa patients, with in each group 26 indolent tumors (ISUP Group1 and pT2) and 26 potentially aggressive tumors (ISUP Group 3-5 and/or pT3). The expression of proteins involved in cholesterol metabolism was analyzed by immunohistochemistry on cancer tissue samples included in tissue microarrays. RESULTS: The amount of cholesterol esters was lower in PPAT from African-Caribbean patients compared with Caucasians, without any correlation with markers of disease aggressiveness. In cancer tissues from African-Caribbean patients, the expression of ABCA1 (involved in cholesterol efflux) was decreased, and that of SREBP-2 (involved in cholesterol uptake) was increased. In both groups of patients, SREBP-2 expression was strongly associated with that of Zeb1, a key player in the epithelial-to-mesenchymal transition (EMT) process. CONCLUSION: These results suggest that cholesterol metabolism differs according to the ethno-geographic origin, in both PPAT and cancer tissues. In African-Caribbeans, the orientation towards accumulation of cholesterol in cancer cells is associated with a more frequent state of EMT, which may promote PCa aggressiveness in this population.

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

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.

A review of new hormonal therapies for prostate cancer in black men: is there enough data?

BACKGROUND: Prostate cancer among black men is known to have specific molecular characteristics, especially the androgen receptor or enzymes related to the androgen metabolism. These targets are keys to the action of new hormonal therapies. Nevertheless, literature has a lack of data regarding black men. We aimed to gather the available literature data on new hormonal therapies among black populations. METHODS: We conducted a literature review from the PubMed / MEDLINE database until October 2020. All clinical studies of new hormonal therapies and black populations, regardless of methodology, were included. RESULTS: Four studies provided data on new hormonal therapies in black populations. Three studies reported a PSA decline in black patients treated with Abiraterone, higher in black men than in white men. Overall survival also appears to be higher in black patients treated with Abiraterone only or first. CONCLUSION: Few articles have evaluated the effectiveness and safety of use of these treatments among black populations. The first results seem to show that Abiraterone can provide a benefit in overall survival in black populations. Prospective studies are needed to answer these questions in the future.

Endocrine disrupting-chemicals and biochemical recurrence of prostate cancer after prostatectomy: A cohort study in Guadeloupe (French West Indies).

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39-4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.

Overall, specific, and metastasis-free survival of Afro-Caribbean men with pathological Gleason 6 prostate cancer.

BACKGROUND: Several studies in the Caucasian population have shown that patients with Gleason 6 prostate cancer, based on surgical specimens, have low or no risk of metastasis. However, there is no data for men of African ancestry. The objective of this study was to estimate the overall, specific, and metastasis-free survival (MFS) of patients with a Gleason 6 score, based on the surgical specimen. PATIENTS AND METHODS: This was a monocentric retrospective study that included 723 consecutive patients treated by radical prostatectomy between 1 January 1 2000 and 31 March 2018, with a Gleason score of 6 based on the surgical specimen. Specific survival (SS) was defined as the time elapsed between surgery and death attributed to prostate cancer. Overall survival was defined as the time elapsed between surgery and death from all causes. The causes of death were verified in the medical records. Survival analyses without biochemical recurrence (BCR) and without salvage treatment were performed according to the Kaplan-Meier method. The Cox model was used for univariate and multivariate analyses. RESULTS: In total, 691 patients were included because 32 were excluded for missing data. Overall 5- and 10-year survival was 94.2% and 87.1%, respectively. SS and MFS were 100%, with a median follow-up of 8.5 years. The BCR rate was 16.5%, with a median time to BCR of 5.1 years. The frequency of salvage treatment was 13.0%, with a median time to surgery of 7.3 years. In univariate analysis, PSA, pathological stage, seminal vesicle invasion, positive margins, and lymph node dissection were significantly associated with an increased risk of BCR and salvage treatment, but only PSA and positive margins were significantly associated by multivariate analysis. DISCUSSION/CONCLUSION: No metastasis or disease-specific deaths were observed for men with Gleason score ≤6 prostate cancer at radical prostatectomy, in particular, men of African ancestry.