scholarly journals Prostate cancer risk in men of differing genetic ancestry and approaches to disease screening and management in these groups

Author(s):  
Jana McHugh ◽  
Edward J. Saunders ◽  
Tokhir Dadaev ◽  
Eva McGrowder ◽  
Elizabeth Bancroft ◽  
...  

AbstractProstate cancer is the second most common solid tumour in men worldwide and it is also the most common cancer affecting men of African descent. Prostate cancer incidence and mortality vary across regions and populations. Some of this is explained by a large heritable component of this disease. It has been established that men of African and African Caribbean ethnicity are predisposed to prostate cancer (PrCa) that can have an earlier onset and a more aggressive course, thereby leading to poorer outcomes for patients in this group. Literature searches were carried out using the PubMed, EMBASE and Cochrane Library databases to identify studies associated with PrCa risk and its association with ancestry, screening and management of PrCa. In order to be included, studies were required to be published in English in full-text form. An attractive approach is to identify high-risk groups and develop a targeted screening programme for them as the benefits of population-wide screening in PrCa using prostate-specific antigen (PSA) testing in general population screening have shown evidence of benefit; however, the harms are considered to weigh heavier because screening using PSA testing can lead to over-diagnosis and over-treatment. The aim of targeted screening of higher-risk groups identified by genetic risk stratification is to reduce over-diagnosis and treat those who are most likely to benefit.

2022 ◽  
Vol 77 ◽  
pp. 102093
Author(s):  
Thanya Pathirana ◽  
Rehan Sequeira ◽  
Chris Del Mar ◽  
James A. Dickinson ◽  
Bruce K. Armstrong ◽  
...  

Author(s):  
Elizabeth K. Bancroft ◽  
Holly Ni Raghallaigh ◽  
Elizabeth C. Page ◽  
Rosalind A. Eeles

Abstract Purpose of Review Prostate cancer (PrCa) is the most common cancer in men in the western world and is a major source of morbidity and mortality. Currently, general population PrCa screening is not recommended due to the limitations of the prostate-specific antigen (PSA) test. As such, there is increasing interest in identifying and screening higher-risk groups. The only established risk factors for PrCa are age, ethnicity, and having a family history of PrCa. A significant proportion of PrCa cases are caused by genetic factors. Recent Findings Several rare germline variants have been identified that moderately increase risk of PrCa, and targeting screening to these men is proving useful at detecting clinically significant disease. The use of a “polygenic risk score” (PRS) that can calculate a man’s personalized risk based on a number of lower-risk, but common genetic variants is the subject of ongoing research. Research efforts are currently focusing on the utility of screening in specific at-risk populations based on ethnicity, such as men of Black Afro-Caribbean descent. Whilst most screening studies have focused on use of PSA testing, the incorporation of additional molecular and genomic biomarkers alongside increasingly sophisticated imaging modalities is being designed to further refine and individualise both the screening and diagnostic pathway. Approximately 10% of men with advanced PrCa have a germline genetic predisposition leading to the opportunity for novel, targeted precision treatments. Summary The mainstreaming of genomics into the PrCa screening, diagnostic and treatment pathway will soon become standard practice and this review summarises current knowledge on genetic predisposition to PrCa and screening studies that are using genomics within their algorithms to target screening to higher-risk groups of men. Finally, we evaluate the importance of germline genetics beyond screening and diagnostics, and its role in the identification of lethal PrCa and in the selection of targeted treatments for advanced disease.


2020 ◽  
Author(s):  
Thanya Pathirana ◽  
Rehan Sequeira ◽  
Chris Del Mar ◽  
James A Dickinson ◽  
Katy J L Bell ◽  
...  

Abstract BackgroundPopulation trends in PSA screening and prostate cancer incidence do not perfectly correspond. We aimed to better understand relationships between trends in PSA screening, prostate cancer incidence and mortality in Australia.MethodsDescription of age standardised time trends in PSA tests, prostate biopsies, cancer incidence and mortality within Australia for the age groups: 45-74, 75-84, and 85+ years.ResultsPSA testing increased from its introduction in 1989 to a peak in 2008. It then declined in men aged 45-84 years. Prostate biopsies and cancer incidence declined from 1995 to 2000, in parallel with decrease in trans-urethral resections of prostate (TURP). After 2000, changes in biopsies and cancer incidence paralleled PSA screening in men 45-84 years, while in men ≥85 years, biopsies stabilised and incidence declined. More recently a reduction in TURP correlated with increased Dutasteride and Tamsulosin usage. Prostate cancer mortality in men aged 45-74 years remained low throughout. Mortality in men 75-84 years gradually increased until the mid 1990s, then gradually decreased. Mortality in men ≥85 years increased until the mid 1990s, then stabilised.ConclusionsAge specific prostate cancer incidence largely mirrors PSA screening rates. Most deviation may be explained by changes in management of benign prostatic disease and incidental cancer detection. The timing of the small mortality reduction in men 75-84 years is more consistent with benefits from advances in treatment than with early detection through PSA. The large increases in prostate cancer incidence with minimal changes in mortality suggest overdiagnosis.


2021 ◽  
Author(s):  
Samuel William David Merriel ◽  
Lucy Pocock ◽  
Emma Gilbert ◽  
Sam Creavin ◽  
Fiona M Walter ◽  
...  

Abstract BackgroundProstate Specific Antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.MethodsA systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.Results563 search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. 19 studies met the inclusion criteria, 18 of which were conducted in secondary care settings (one from a screening study cohort). All studies used histology obtained by Transrectal Ultrasound guided biopsy (TRUS) as a reference test, usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the receiving-operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.ConclusionsCurrently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 115-115
Author(s):  
Robert Scott Libby ◽  
Hoang MT Nguyen ◽  
Jordan J. Kramer ◽  
Allison H. Feibus ◽  
Raju Thomas ◽  
...  

115 Background: Many men with an initial negative prostate biopsy have a persistently elevated prostate specific antigen (PSA) prompting physicians to perform repeat biopsies. African American men (AA) are at particular risk as they have a greater prostate cancer (PCa) incidence and mortality, yet traditional PSA testing may be less reliable in this cohort. We sought to determine the predictors of PCa and PCa severity in a racially diverse population on subsequent biopsy following an initial benign biopsy. Methods: Upon receiving Institutional Review Board approval, a retrospective analysis was performed on men with repeat prostate biopsies at Tulane Medical Center and Southeast Louisiana Veterans Health Care Services in New Orleans, Louisiana from 2003-2015. Inclusion criteria included patients with a benign initial prostate biopsy and underwent subsequent repeat prostate biopsy within 5 years. Race, age, serum PSA, PSA density (PSAD), and prostate volume by transrectal ultrasound (TRUS) were evaluated to determine if they correlate with the presence and severity of PCa. Aggressive PCa was defined as Gleason score >6. Results: A total of 209 men were included; 127 (61%) were AA, and 82 (39%) were Caucasian American men (CA). The two groups were similar with respect to PSA, PSAD, and TRUS. More AA (25.2% vs. 17.1%) had a repeat biopsy showing any PCa. Of those with PCa, 28.1% of AA and 28.6% of CA had aggressive PCa. PSAD positively correlated with any PCa (p=.015). TRUS negatively correlated with any PCa (p=.008). PSA levels (p<.001) and PSAD (p<.001) positively correlated with aggressive PCa in CA but not in AA. Conclusions: The goal of prostate biopsy particularly for those with a prior negative biopsy is to detect aggressive PCa. PSA and PSAD positively correlated with finding any PCa in both AA and CA but not with aggressive PCa in AA. PSA and PSAD are less accurate predictors of aggressive PCa in AA, and novel biomarkers are needed. [Table: see text]


2017 ◽  
Vol 117 (8) ◽  
pp. 1128-1136 ◽  
Author(s):  
Alicia C. McDonald ◽  
Clareann H. Bunker ◽  
Jay Raman ◽  
John Richie ◽  
Alan L. Patrick

AbstractBlack men are known to have a higher risk for prostate cancer (PC). Carotenoids and retinol, linked to PC, have not been compared in different black populations at risk. We examined serum carotenoid and retinol levels between PC-free African-Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and African-American (AA) men with elevated serum prostate-specific antigen (PSA) levels (≥4 ng/ml). AC men who participated in the 2003 lycopene clinical trial and AA men who participated in the 2001–2006 National Health and Nutrition Examination Survey were compared. Serum specimens were analysed for carotenoid (β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to examine the association between serum carotenoid and retinol levels and black ethnicity, overall and among men with elevated serum PSA. There were sixty-nine AC men and sixty-five AA men, aged 41–79 years, included. AC men were associated with lower serum lycopene and retinol levels, and higher serum α- and β-carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for age, BMI, ever smoked cigarettes, education and hypertension (P≤0·03). Among men with elevated PSA, serum retinol was no longer statistically significant with ethnicity (P=0·06). Possible differences may be attributed to dietary intake, genetics and/or factors that influence bioavailability of these micronutrients. Prospective studies are warranted that investigate whether these differences in micronutrients between AC Tobagonian and AA men influence PC risk.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249009
Author(s):  
Carlos Anselmo Lima ◽  
Brenda Evelin Barreto da Silva ◽  
Evânia Curvelo Hora ◽  
Marcela Sampaio Lima ◽  
Erika de Abreu Costa Brito ◽  
...  

Prostate cancer differently affects different regions of the world, displaying higher rates in more developed areas. After the implementation of prostate-specific antigen (PSA) testing, several studies described rising rates globally, but it is possible that indolent lesions are being detected given the lack of changes in mortality data. The Brazilian government recommends against PSA screening in the male population regardless of age, but the Urology Society issued a report recommending that screening should start at 50 years old for certain men and for those aged ≥75 years with a life expectancy exceeding 10 years. In this study, we examined the incidence and mortality rates of invasive prostate cancer over time in the Sergipe state of Brazil. The databases of the Aracaju Cancer Registry and Mortality Information System were used to calculate age-standardized rates for all prostate tumors (International Classification of Diseases 10th edition: C61 and D07.5) in the following age ranges: 20–44, 45–54, and ≥65 years. We identified 3595 cases of cancer, 30 glandular intraepithelial high-grade lesions, and 3269 deaths. Using the Joinpoint Regression Program, we found that the incidence of prostate cancer dramatically increased over time until the mid-2000s for all age groups, after which the rates declined. Prostate cancer mortality rates increased until 2005, followed by a non-significant annual percent change of 22.0 in 2001–2005 and a stable rate thereafter. We noticed that the increases and decreases of the incidence rates of prostate cancer were associated with the screening recommendations. Meanwhile, the increased mortality rates did not appear to be associated with decreased PSA testing; instead, they were linked to the effects of age and improvements in identification of the cause of death. Thus, we do not believe a PSA screening program would benefit the population of this study.


2018 ◽  
Vol 12 (6) ◽  
pp. 1807-1823 ◽  
Author(s):  
Harold Evelyn Taitt

Although research has reported that prostate cancer (PCa) incidence and mortality rates are among the highest for African Americans, the data is inconclusive regarding PCa rates in native African men, Black men residing in other countries, and men in Asia, Europe, and the Americas. Data reveals that prostate-specific antigen (PSA) testing and disease incidence have risen significantly in developing and Asian countries, and PCa has become one of the leading male cancers in many of those nations. The objective of this study was to review published peer-reviewed studies that address PCa in different regions of the world to get a better understanding of how PCa incidence, prevalence, detection, and mortality are influenced by race, ethnicity, and geography. A secondary goal was to compare PCa data from various world regions to contextualize how disproportionate the incidence and mortality rates are among men from the African diaspora versus men of European, Hispanic, and Asian descent, as well as to highlight the need for more robust screening and treatment guidelines in developing countries. There are differences in incidence and mortality rates between men of African, Asian, Hispanic, and European ancestry, confirming the involvement of genetic factors. However, differences between men of the same race and ethnicity who live in different countries suggest that environmental factors may also be implicated. Availability and access to diagnostic and health-care services as well as recommendations regarding PCa testing vary from country to country and contribute to the variability in incidence and mortality rates.


2021 ◽  
Vol 11 ◽  
Author(s):  
Sanny Kappen ◽  
Geertruida H. de Bock ◽  
Eunice Sirri ◽  
Claudia Vohmann ◽  
Joachim Kieschke ◽  
...  

BackgroundProstate cancer (PCa) is the most frequent cancer among men in Europe. Differences in PCa incidence around the world can be partly explained by variations in recommendations for prostate-specific antigen (PSA), particularly for early detection. For example, the PSA testing policy is more conservative in the Netherlands than in Germany. To better understand the relationship between PSA testing recommendations and PCa incidence, stage distribution, and mortality, we compared these variables over time between Lower Saxony in northwestern Germany and the neighboring province of Groningen in the Netherlands.MethodsPopulation data, tumor stage- and age group-specific PCa incidence (ICD-10 C61) and mortality rates for Lower Saxony and Groningen were obtained from the Lower Saxony Epidemiological Cancer Registry, the Netherlands Comprehensive Cancer Organization, and Statistics Netherlands for 2003–2012. Incidence and mortality rates per 100,000 person-years were age-standardized (ASR, old European standard). Trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR) for specific age groups were assessed using joinpoint regression.ResultsThe mean annual PCa ASIR between 2003 and 2012 was on average 19.9% higher in Lower Saxony than in Groningen (120.5 vs. 100.5 per 100,000), while the mean annual ASMR was on average 24.3% lower in Lower Saxony than in Groningen (21.5 vs. 28.4 per 100,000). Between 2003 and 2012, the average annual percentage change (AAPC) in PCa incidence rates did not change significantly in either Lower Saxony (−1.8%, 95% CI −3.5, 0.0) or Groningen (0.2%, 95% CI −5.0, 5.7). In contrast, the AAPC in mortality rate decreased significantly during the same time period in Lower Saxony (−2.5%, 95% CI −3.0, −2.0) but not in Groningen (0.1%, 95% CI −2.4, 2.6).ConclusionsHigher PCa incidence and lower PCa-related mortality was detected in Lower Saxony than in Groningen. Although recommendations on PSA testing may play a role, the assessed data could not offer obvious explanations to the observed differences. Therefore, further investigations including data on the actual use of PSA testing, other influences (e.g., dietary and ethnic factors), and better data quality are needed to explain differences between the regions.


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