scholarly journals Updates in Prostate Cancer Research and Screening in Men at Genetically Higher Risk

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.

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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Matthew R. Cooperberg ◽  
Paul Brendel ◽  
Daniel J. Lee ◽  
Rahul Doraiswami ◽  
Hariesh Rajasekar ◽  
...  

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]


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

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jae Yoon Kim ◽  
Ji Hyeong Yu ◽  
Luck Hee Sung ◽  
Dae Yeon Cho ◽  
Hyun-Jung Kim ◽  
...  

Abstract Background We aimed to evaluate the usefulness of the Beckman Coulter prostate health index (PHI) and to compare it with total prostate-specific antigen (PSA) levels and related derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in the Korean population. Methods A total of 140 men who underwent their first prostate biopsy for suspected PCa were included in this prospective observational study. The diagnostic performance of total PSA, free PSA, %free PSA, [–2] proPSA (p2PSA), %p2PSA, and PHI in detecting and predicting the aggressiveness of PCa was estimated using the receiver operating characteristic curve (ROC) and logistic multivariate regression analyses. Results Of 140 patients, PCa was detected in 63 (45%) of participants, and 48 (76.2%) of them had significant cancer with a Gleason score (GS) ≥ 7. In the whole group, the area under the curve (AUC) for ROC analysis of tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.63, 0.57, 0.69, 0.69, 0.72, and 0.76, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p = 0.005). For PCa with GS ≥ 7, the AUCs for tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.62, 0.58, 0.41, 0.79, 0.86, and 0.87, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p < 0.001). In the subgroup with tPSA 4–10 ng/mL, both %p2PSA and PHI were strong independent predictors for PCa (p = 0.007, p = 0.006) and significantly improved the predictive accuracy of a base multivariable model, including age, tPSA, fPSA and %fPSA, using multivariate logistic regression analysis. (p = 0.054, p = 0.048). Additionally, at a cutoff PHI value > 33.4, 22.9% (32/140) of biopsies could be avoided without missing any cases of aggressive cancer. Conclusions This study shows that %p2PSA and PHI are superior to total PSA and %fPSA in predicting the presence and aggressiveness (GS ≥ 7) of PCa among Korean men. Using PHI, a significant proportion of unnecessary biopsies can be avoided.


Author(s):  
Ciara O’Hanlon Brown ◽  
Jonathan Waxman

Prostate cancer is the most common cancer to effect men and the second most common cause of cancer-related death. Premalignant change or prostatic intraepithelial neoplasia has been detected within the prostate glands of men under 30 years of age. The incidence of prostate cancer remains negligible until men reach their 40s from whence it rises steadily and by 80 years 70% of men have detectable tumours at autopsy (1). A majority of prostate cancers arise from the peripheral zone of the prostate and rarely cause obstructive symptoms. Consequently, prostate cancers have historically presented late, with symptoms of metastatic disease. The advent of prostate-specific antigen (PSA) testing has produced a stage shift so that at present over 90% of prostate cancers are diagnosed as organ-confined disease. PSA diagnosis has unmasked a subset of prostate tumours that exhibit an indolent growth pattern and appear destined to remain organ-confined tumours the patient dies with, and not from. US SEER data estimates a 50-year-old man has a 42% chance of developing prostate cancer but only a 3.6% chance of dying from the disease. Features, either clinical or molecular, which would allow clinicians to clearly differentiate indolent from aggressive disease while still at the organ-confined stage, have yet to be identified (1). Adenocarcinoma is the predominant histological subtype of prostate cancer, accounting for 95% of tumours. Prostatic adenocarcinomas arise from androgen receptor-positive epithelial cells. On histological examination, prostate cancers appear multifocal and demonstrate heterogeneity both within individual tumours and across populations. This has created an obstacle as researchers attempt to subclassify prostate cancer and identify the molecular defects responsible for driving prostatic carcinogenesis (1). Of prostate cancers, 80–90% are androgen receptor-positive at diagnosis (2), thus to date the androgen–androgen receptor axis is the sole molecular feature of this disease that has been successfully harnessed as a therapeutic target.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1064 ◽  
Author(s):  
Sebastian Chakrit Bhakdi ◽  
Prapat Suriyaphol ◽  
Ponpan Thaicharoen ◽  
Sebastian Tobias Karl Grote ◽  
Chulaluk Komoltri ◽  
...  

Even though more than 350,000 men die from prostate cancer every year, broad-based screening for the disease remains a controversial topic. Guidelines demand that the only commonly accepted screening tool, prostate-specific antigen (PSA) testing, must be followed by prostate biopsy if results are elevated. Due to the procedure’s low positive predictive value (PPV), however, over 80% of biopsies are performed on healthy men or men with clinically insignificant cancer—prompting calls for new ways of vetting equivocal PSA readings prior to the procedure. Responding to the challenge, the present study investigated the diagnostic potential of tumour-associated circulating endothelial cells (tCECs), which have previously been described as a novel, blood-based biomarker for clinically significant cancers. Specifically, the objective was to determine the diagnostic accuracy of a tCEC-based blood test to detect clinically significant prostate cancer (defined as Gleason score ≥ 3 + 4) in high-risk patients. Performed in a blinded, prospective, single-centre set-up, it compared a novel tCEC index test with transrectal ultrasound-guided biopsy biopsy as a reference on a total of 170 patients and found that a tCEC add-on test will almost double the PPV of a standalone PSA test (32% vs. 17%; p = 0.0012), while retaining a negative predictive value above 90%.


Author(s):  
Ian M. Thompson

Overview: Prostate cancer is a ubiquitous disease, affecting as many as two-thirds of men in their 60s. Through widespread prostate-specific antigen (PSA) testing, increasing rates of prostate biopsy, and increased sampling of the prostate, a larger fraction of low-grade, low-volume tumors have been detected, consistent with tumors often found at autopsy. These tumors have historically been treated in a manner similar to that used for higher-grade tumors but, more recently, it has become evident that with a plan of active surveillance that reserves treatment for only those patients whose tumors show evidence of progression, very high disease-specific survival can be achieved. Unfortunately, the frequency of recommendation of an active surveillance strategy in the United States is low. An alternative strategy to improve prostate cancer detection is through selected biopsy of those men who are at greater risk of harboring high-grade, potentially lethal cancer. This strategy is currently possible through the use of risk assessment tools such as the Prostate Cancer Prevention Trial Risk Calculator ( www.prostate.cancer.risk.calculator.com ) as well as others. These tools can predict with considerable accuracy a man's risk of low-grade and high-grade cancer, allowing informed decision making for the patient with a goal of detection of high-risk disease. Ultimately, other biomarkers including PCA3, TMPRSS2:ERG, and [-2]proPSA will likely aid in discriminating these two types of cancer before biopsy.


AAOHN Journal ◽  
1998 ◽  
Vol 46 (8) ◽  
pp. 379-384 ◽  
Author(s):  
Claire Snyder ◽  
Peggy N. Schrammel ◽  
Claudia B. Griffiths ◽  
Robert I. Griffiths

Recognition of the mortality and morbidity associated with prostate cancer has resulted in employer based screening programs. This retrospective cohort study identified the employer costs of prostate cancer screening and referrals due to abnormal test results. The subjects were 385 men enrolled in a workplace screening program at a single employer between 1993 and 1995. Screening consisted of digital rectal examination (DRE) annually for enrolled employees aged 40 years and older, plus annual prostate specific antigen (PSA) testing for those 50 and older, and those 40 and older and considered at high risk. Data related to the health care and lost productivity costs of screening and referrals for abnormal test results were collected and analyzed. The total cost of screening was $44,355, or approximately $56 per screening encounter (788 DREs; 437 PSAs). Abnormal screening tests resulted in 52 referrals. Upon further evaluation, 42% were found to have an enlargement, 29% a node, and 12% benign prostatic hyperplasia. Only one malignancy was found. The total cost of additional referrals was $31,815, or 42% of the cost of screening plus referrals. As the cost per screening encounter was low, prostate cancer screening in the workplace is an efficient alternative.


2008 ◽  
Vol 4 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Kamilah B. Thomas ◽  
Sean L. Simpson ◽  
Will L. Tarver ◽  
Clement K. Gwede

African American and White men have the highest rates of prostate cancer in the United States. Families represent important social contexts within which illness occurs.The purpose of this study is to explore whether prostate-specific antigen (PSA) testing is associated with instrumental and informational social support from family members among a sample of Black and White men aged 45 and older. Data from the 2005 Health Information National Trends Survey were analyzed using logistic regression. The dependent variable was having a PSA test within the past year or less. The independent variables consisted of selected demographic and family informational and instrumental social support variables. The statistically significant variables included age and having a family member with cancer. Additional studies to elucidate the mechanisms of social support from family for prostate cancer are needed.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Daniel W. Smith ◽  
Diliana Stoimenova ◽  
Khadijah Eid ◽  
Al Barqawi

Prostate cancer is one of the most prevalent cancers among men in the United States, second only to nonmelanomatous skin cancer. Since prostate-specific antigen (PSA) testing came into widespread use in the late 1980s, there has been a sharp increase in annual prostate cancer incidence. Cancer-specific mortality, though, is relatively low. The majority of these cancers will not progress to mortal disease, yet most men who are diagnosed opt for treatment as opposed to observation or active surveillance (AS). These men are thus burdened with the morbidities associated with aggressive treatments, commonly incontinence and erectile dysfunction, without receiving a mortality benefit. It is therefore necessary to both continue investigating outcomes associated with AS and to develop less invasive techniques for those who desire treatment but without the significant potential for quality-of-life side effects seen with aggressive modalities. The goals of this paper are to discuss the problems of overdiagnosis and overtreatment since the advent of PSA screening as well as the potential for targeted focal therapy (TFT) to bridge the gap between AS and definitive therapies. Furthermore, patient selection criteria for TFT, costs, side effects, and brachytherapy template-guided three-dimensional mapping biopsies (3DMB) for tumor localization will also be explored.


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