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.

Tumour-based Mutational Profiles Predict Visceral Metastasis Outcome and Early Death in Prostate Cancer Patients.

BACKGROUND: Visceral metastases are known to occur in advanced prostate cancer, usually when the tumour is resistant to androgen deprivation and, have worse outcomes regardless of therapies. OBJECTIVE: To analyse genomic alterations in tumour samples according to their lymphatic, bone, and visceral metastatic stages and overall survival. DESIGN, SETTING, AND PARTICIPANTS: We selected 200 patients with metastatic prostate cancer. Genomic profiling of 111 genes and molecular signatures (homologous recombination deficiency [HRD], microsatellite instability, and tumour burden mutation) was performed with the MyChoice test (Myriad Genetics, Inc, Salt Lake City, UT, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association between genomic profiles and visceral metastatic evolution was evaluated using logistic regression. Kaplan-Meier and Cox proportional hazard analyses were used for analyses of early death. RESULTS AND LIMITATIONS: A total of 173 (87%) genomic profiles were obtained. Eighty-four (49%) patients died during the follow-up period (median duration = 76 mo). TP53 was the most frequently mutated gene, followed by FANC genes, including BRCA2, and those of the Wnt-pathway (APC/CTNNB1). TP53 gene mutations were more frequent in patients of European (42%) than in those of African (16%) ancestry. An HRD score of >25 was predictive of FANC gene mutations. The mutational status of TP53 (p < 0.001) and APC (p = 0.002) genes were significantly associated with the risk of visceral metastases. The mutational status of CTNNB1 (p = 0.001), TP53 (p = 0.015), BRCA2 (p = 0.027), and FANC (p = 0.005) genes were significantly associated with an earlier age at death. The limitations are the retrospective study design based on a selection of genes and the low frequency of certain molecular events. CONCLUSIONS: Mutations in the TP53 gene and genes (APC/CTNNB1) related to the Wnt pathway are associated with metastatic visceral dissemination and early death. These genomic alterations could be considered as markers to identify prostate cancer patients at a high risk of life-threatening disease who might benefit from more intensified treatment or new targeted therapies. PATIENT SUMMARY: In this report, we evaluated the relationships between genomic profiles (gene mutations and molecular signatures) of tumour samples from patients with metastatic prostate cancer and early death. We found that mutations of specific genes, notably TP53 and APC/CTNNB1 related to the Wnt pathway, are associated with visceral metastatic progression and an earlier age at death.

Prostate biopsy approach and complication rates.

Prostate biopsy is the gold standard to confirm prostate cancer. In addition to standard 12-core biopsies, magnetic resonance imaging (MRI)-guided prostate biopsies have recently been introduced to improve the detection of clinically significant prostate cancer. The present study aimed to compare the complications after standard transrectal ultrasound-guided and standard plus targeted (MRI-guided) prostate biopsies, to study the impact of the number of biopsy cores on complication rates, and to compare complication rates after transrectal ultrasound-guided prostate biopsies with those following transperineal prostate biopsies from the literature. A prospective study was performed, which included 135 patients who underwent transrectal ultrasound-guided prostate biopsies between April 1 and June 30, 2022, at the Urology Department of the University Hospital of Pointe à Pitre (Pointe à Pitre, Guadeloupe). A total of 51 patients were excluded because of missing information concerning their post-biopsy surveillance. The median age at the time of biopsy was 69 years, median prostate-specific antigen value was 8.9 ng/ml, median prostate volume was 57.5 ml, and median number of cores was 15. A total of 35 of the 84 included patients (41.7%) had a standard biopsy only and 49 (58.3%) had targeted (MRI-guided) plus standard biopsies. A total of 53 patients (63.1%) experienced early side effects, whereas only 24 patients (28.6%) experienced late side effects. Three patients (3.6%) required hospitalization for post-biopsy complications. Early side effects, especially hematuria and hematospermia, occurred significantly more frequently in the targeted plus standard group, with more cores taken, with no significant difference concerning late side effects or infectious complications between the standard and standard plus targeted groups. The admission rate for sepsis after transperineal biopsy has been reported to vary between 0 and 1%, whereas the present study had an admission rate of 2.29% using the transrectal approach. Further studies are required to analyze the complications requiring hospitalization after transrectal and transperineal biopsies.

Simplified antibiotic guidelines in urology are associated with decreased multidrug-resistant Enterobacterales.

PURPOSE: A simplified therapeutic guideline (STG) was established in our urology ward in 2019 for urinary infections. Our aim was to describe the level of physician adherence to STG and the impact of a limited number of antibiotic compounds on the rate of multidrug-resistant (MDR) bacteria. As guidelines should improve patient care, unfavorable outcomes were also reported. METHODS: The STG for community-acquired and nosocomial urinary infections, including six antibiotics, was established in November 2019 and has been officially applied since January 2020. Treatment duration has to be ≤14 days. We conducted a before-after study to measure physician adherence to the STG for bacteremia treatment between January 2017 and December 2022. Adherence was defined as exclusive use of STG antibiotics. All isolated bacteria from blood cultures were recorded, including MDR Enterobacterales, defined as AmpC ß-lactamase- or ESBL-producing strains. Unfavorable outcomes were defined as uncontrolled infection, a second surgical procedure, ICU requirement, and/or death. RESULTS: Seventy-six cases of bacteremia occurred between January 2017 and December 2019, and ninety between January 2020 and December 2022. The main comorbid condition was urological cancer (46%). The main reason for surgery was ureteral stent (32%). Antibiotic management in accordance with STG increased from 18% to 52%, p < 0.001, and treatments > 14 days decreased from 53% to 28%, p < 0.001. MDR Enterobacterales bacteremia was reduced from 52% to 35%, p = 0.027. The rate of unfavorable outcomes was unchanged. CONCLUSION: STG adherence in urology was satisfactory and associated with reduced MDR Enterobacterales bacteremia.

Persistent organochlorine pesticides in periprostatic adipose tissue from men with prostate cancer: Ethno-geographic variations, association with disease aggressiveness.

Although several studies have examined the relationship between organochlorine pesticides (OCPs) and prostate cancer (PCa) risk, no data are available concerning the association between OCPs concentrations in periprostatic adipose tissue (PPAT), which reflects cumulative exposure, and PCa aggressiveness. Moreover, no previous study has compared OCPs exposure in two distinct ethno-geographical populations. The objectives were to analyze OCPs in PPAT of PCa patients from either Mainland France or French West Indies in correlation with features of tumor aggressiveness, after adjusting for potential confounders such age, BMI, and polyunsaturated fatty acid (PUFA) content of PPAT. PPAT was analyzed in 160 patients (110 Caucasians and 50 African-Caribbeans), 80 with an indolent tumor (ISUP group 1 + pT2), and 80 with an aggressive tumor (ISUP group more than 3 + pT3). The concentrations of 29 OCPs were measured in PPAT concomitantly with the characterization of PUFA content. Exposure patterns of OCPs differed according to the ethno-geographical origin. Most OCPs were found at higher concentration in Caucasian patients, whereas pp'-DDE content was twice as high in African-Caribbeans. Chlordecone was only detected in PPAT from African-Caribbean patients. Most OCP concentrations were positively correlated with age, and some with BMI. After adjusting for age, BMI, and PUFA composition of PPAT, no significant association was found between OCPs content and risk of aggressive disease, except of mirex which appeared inversely associated with aggressive features of PCa in Caucasian patients. These results highlight a significant ethno-geographic variation in internal exposure to OCPs, which likely reflects differences in consumption patterns. The inverse relationship observed between mirex concentration and markers of PCa aggressiveness need to be further investigated.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry.

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

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.

Biopsy Grade Group as a reliable prognostic factor for BCR in Afro-Caribbean men with intermediate- and high-risk prostate cancer.

PURPOSE: The Grade Group (GG) classification is recommended by guidelines as a reliable prognostic factor of prostate cancer. However, most studies have been performed on the Caucasian population. Our objective was to validate GG classification as a safe way to classify intermediate- and high-risk patients with African ancestry. PATIENTS AND METHODS: This was a retrospective study in an Afro-Caribbean population. A total of 1236 patients were included between 2000 and 2015. Patients were stratified according to (GG). Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analyses using the Cox model. RESULTS: There was no significant difference at 5 and 10-year BCR-free survival between the intermediate- and high-risk groups, based on the D'Amico classification. There was a highly significant difference in BCR-free survival at 5 (p < 0.0001) and 10 years (p < 0.0001) for patients of GG 1 and 2 vs 3, 4, and 5, respectively. There was no significant difference in 5-year BCR-free survival of patients of GG grades 1 and 2, whether lymph-node dissection was performed or not. There was a significant difference between GG 2 and 3 patients in 5 (p = 0.008) and 10-year BCR-free survival (p = 0.01). High PSA (p < 0.0001), pathological GG ≥ 3 (p < 0.0001), pathological stage pT3 (p < 0.0001) and positive margins (p < 0.0001) were factors for BCR in multivariate analysis. CONCLUSION: The GG 2015 classification appears to be a better prognostic factor than D'Amico classification for intermediate- and high-risk Afro-Caribbean patients.

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.

Mutational Profile of Aggressive, Localised Prostate Cancer from African Caribbean Men Versus European Ancestry Men.

Causes of high mortality of prostate cancer in men of African ancestry living in the French West Indies are still debated, between suspicions of environmental factors and genetic susceptibility. We report an integrated genomic study of 25 tumour tissues from radical prostatectomy of aggressive (defined by International Society of Urological Pathology ≥3) prostate cancer patients (10 African Caribbean and 15 French Caucasian) using single nucleotide polymorphism arrays, whole-genome sequencing, and RNA sequencing. The results show that African Caribbean tumours are characterised by a more frequent deletion at 1q41-43 encompassing the DNA repair gene PARP1, and a higher proportion of intrachromosomal rearrangements including duplications associated with CDK12 truncating mutations. Transcriptome analyses show an overexpression of genes related to androgen receptor activity in African Caribbean tumours, and of PVT1, a long non-coding RNA located at 8q24 that confirms the strong involvement of this region in prostate tumours from men of African ancestry. Patient summary: Mortality of prostate cancer is higher in African Caribbean men than in French Caucasian men. Specificities of the former could be explained by genomic events linked with key genes such as DNA damage pathway genes PARP1, CDK12, and the oncogenic long non-coding RNA gene PVT1 at the 8q24 prostate cancer susceptibility locus.