Prostate-specific Antigen Testing Research Articles

Abstract A027: Systematic review of real-world adherence to blood-based laboratory tests for average-risk disease screening: potential implications for emerging colorectal cancer screening modalities

Abstract Introduction: Blood-based tests represent a compelling option for early detection and management of cancers and other chronic diseases. While blood-based tests may offer potential to increase patient engagement, the assumption of greater adherence in clinical practice requires further evaluation. This systematic review aimed to evaluate the real-world adherence to established blood-based tests for commonly recommended screening indications, to better inform expectations for proposed application to average-risk colorectal cancer (CRC) screening. Methods: A systematic search of PubMed, Embase, and citations was performed to identify literature published from 2010 to 2023. Studies examined adherence to routine blood-based laboratory tests with a Grade A or B recommendation per the United States Preventive Services Task Force (USPSTF) for diabetes, dyslipidemia, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) in an average-risk patient population were included. In addition, prostate-specific antigen (PSA) testing adherence for prostate cancer screening (Grade-C USPSTF recommendation), the only commonly accessible blood-based single-cancer screening test for average-risk adults, was also included. Studies without venipuncture-derived blood were excluded. Results: Of 53,067 articles screened, 69 were included in the analysis. Overall, adherence rates of blood-based tests were highly variable, with median values (interquartile range, IQR) of 66.3% (11.8%), 67.8% (18.0%), 34% (28.7%), and 36.8% (30%) for diabetes, dyslipidemia, HCV, and HIV, respectively. PSA testing adherence was 37.2% (18.4%). Beyond disease type, adherence varied by study design, data source, patient characteristics, clinical setting, and study country. Information and selection bias were the most common risks of bias. Conclusions: Based on data from this comprehensive systematic review, real-world adherence to currently recommended, blood-based screening strategies is suboptimal. Future research is needed to identify the extent to which these data are generalizable to blood-based CRC screening, and to determine if/how this candidate strategy would impact clinical, economic, and health equity outcomes. Citation Format: Quang A. Le, Takako Kiener, Heather A. Johnson, Rukaiyya S. Khan, Joyce Kong, Kevin H. Li, Gina Thompson, A. Burak Ozbay, Mallik Greene, Paul J. Limburg, A. Mark Fendrick, John B. Kisiel, Derek W. Ebner. Systematic review of real-world adherence to blood-based laboratory tests for average-risk disease screening: potential implications for emerging colorectal cancer screening modalities [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A027.

Abstract A003: CD45 positive circulating tumor cells as a prognostic marker in prostate cancer

Abstract Prostate cancer is one of the most common types of cancer among male patients worldwide, making early diagnosis and effective treatment crucial for improving patient survival rates. In this regard, circulating tumor cells (CTCs) have garnered attention as an important biomarker for cancer staging and monitoring treatment response. In prostate cancer, CTCs are typically identified as keratin+/CD45- cells, with additional markers such as PSA or PSMA also being used. The conventional CTC identification way have dismissed CD45+/keratin+ double-positive cells as artifacts by nonspecific binding during the staining process. However, recent studies have reported the presence of CD45+/keratin+ CTCs in various types of cancers, highlighting metastatic potential and their ability to evade the immune system. These findings require re- examination of the role for the double positive CTCs. Therefore, this study aimed to identify the presence of CD45+ CTCs in prostate cancer and to assess their clinical significance. Blood samples were collected from 80 prostate cancer patients, followed by unbiased isolation of CTCs, which were stained using PSA, keratin, and CD45. The detected CTCs were categorized based on CD45 expression, and the clinical relevance of each group was validated using patient information. Through this study, we aimed to confirm whether the CD45+ CTCs can be a clinical indicator in prostate cancer. The results revealed that CD45+ CTCs accounted for 90% of all detected CTCs, likely due to their high immune evasion capabilities. Additionally, in 17% of the patients, only CD45+ CTCs were detected, indicating the potential to expand CTC detection even in patients where CTCs were previously undetected using conventional criteria. The number of CD45+ CTCs was significantly higher in patients with progressive disease compared to those with complete or partial response, showing greater statistical significance than analyses using CD45- CTCs. Furthermore, the number of PSA+ CTCs was closely linked to changes in plasma PSA levels, suggesting they could be used as a supporting marker to enhance the accuracy of current plasma PSA tests. These findings indicate that CD45+ CTCs in prostate cancer are not merely artifacts of nonspecific binding but are indeed meaningful cells closely related to cancer progression. This study suggests that CD45+ CTCs have the potential to be utilized as a prognostic biomarker in prostate cancer. By including CD45+ CTCs, which were previously overlooked in conventional CTC analysis methods, more sensitive and accurate cancer monitoring could be achieved. In-depth future studies on the clinical applicability of CD45+ CTCs could significantly contribute to predicting prognosis and developing personalized treatment strategies for prostate cancer patients. Citation Format: Hyeongjung Woo, Woon-Hae Kim, Hyun Young Shin, Hyerin Jung, Hyung Ho Lee, Minseok S. Kim, Jae Young Joung. CD45 positive circulating tumor cells as a prognostic marker in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A003.

Small area estimation of prostate-specific antigen testing in U.S. states and counties.

In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended against prostate cancer screening using the prostate-specific antigen (PSA) test for all age groups. In 2018 the USPSTF's recommendation shifted from a "D" (not recommended) to a "C" (selectively offering PSA-based screening based on professional judgment and patient preferences) in men ages 55-69. Limited reliable county-level prostate cancer screening data is available for cancer surveillance purposes. Utilizing data from the National Health Interview Survey (NHIS) and Behavioral Risk Factor Surveillance System (BRFSS) collected in 2012-2019, state- and county-level small area models were developed for estimating PSA testing. Model diagnosis, internal validation, and external validation examining associations of PSA testing and prostate cancer incidence were conducted. Model-based estimates of PSA testing rate were produced for all U.S. states and 3,142 counties for two data periods: 2012-2016 and 2018-2019. Geographic variations across counties were demonstrated through maps. Moderate positive correlations between PSA-based screening and prostate cancer incidence were observed, for example, the state-level weighted Pearson's correlation coefficients were 0.5025 (p-value=0.0002) and 0.3691 (p-value=0.0077) for 2012-2016 and 2018-2019, respectively. These modeled estimates showed improved precision and adjusted for the differences between BRFSS and NHIS. The approach of combining NHIS and BRFSS utilized strengths of the larger sample size of BRFSS and generally higher response rates and better household coverage from the NHIS. The resulting small area estimates offer a valuable resource for the cancer surveillance community, aiding in targeted interventions, decision-making, and further research endeavors.

Risks associated with cancer screening programmes among multimorbid patients: a systematic review

Abstract Background Cancer screening programmes have been implemented to facilitate early detection of cancer. However, there are risks associated with cancer screening, such as overdiagnosis. This means identifying problems that were never going to cause harm1. This includes identification of abnormalities that do not progress, or that progress too slowly to cause symptoms or harm during a person’s remaining lifetime in the context of multi-morbidity1,2. Aim We conducted a systematic review of the literature to explore the harms associated with overdiagnosis in multimorbid patients when they undergo three different types of cancer screening programmes. Methods The search was conducted on MEDLINE, EMBASE, PSYCHINFO and Scopus from 1960 (cancer screening programmes implementation) until November 2023. Inclusion criteria involved studies with multimorbid participants (having two or more chronic conditions), having one of three common types of cancers (i.e., breast, prostate and lung), and used a standardised method for screening (i.e., mammography, Prostate-specific antigen test, and Low Dose Computed tomography (LDCT) or Computed Tomography scans (CT)). Only peer-reviewed studies published in English were included. Four keyword sets were used, “Multimorbidity”, “Overdiagnosis “, “Patient harms” and “Cancer screening”. Two independent reviewers conducted the search and data extraction. Rayyan web application was used to help with title, and abstract screening, and to compare the independent reviews. The Newcastle-Ottawa scale was used for quality assessment. This systematic review was registered with PROSPERO database (CRD42024475175) and followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidance. Ethical approval was not required to undertake this review. Results A total of 200 studies resulted from all the databases search and duplicates (n=29) removed. Titles, abstracts and full-texts were screened, with seven studies meeting the inclusion criteria. Quality assessment of the included studies showed two studies of good quality and five studies of poor quality. All included studies were conducted in the United States. Breast cancer overdiagnosis increased with increasing the number of comorbidities. Rates of overdiagnosis with prostate cancer were higher compared to breast cancer, with multimorbid patients having a 15% higher risk of overdiagnosed malignancies, compared to non-multimorbid individuals. Harms of overdiagnosis were categorised into psychological (e.g. anxiety), physical (e.g. side effects of medications) and financial (e.g. costs to healthcare systems). Overdiagnosis with lung cancer was associated with increased anxiety, with more individuals dying from other causes than lung cancer in post-mortem studies, questioning the risk versus benefit of lung cancer screening result interpretation for non-progressive disease. Conclusion The emergence of sophisticated testing technologies and greater access to screening tests can contribute to overdiagnosis. We found many different types of harm related to overdiagnosis in common types of cancer. Further research is required to explore the risk of overdiagnosis with other types of cancer. Awareness of clinicians about the risks of overdiagnosis, particularly in high-risk population, such as multimorbid patients, could guide their decision-making regarding non-progressive cancer treatment.

Commercial prices and their influence on urology practices: Prostate cancer care among men with Medicare.

For men with prostate cancer, there is substantial variation in the use of conservative management, such as active surveillance. Commercial prices, which vary across urology practices, may afford incentives that foster physician behaviors associated with utilization. Such behaviors may "spillover" to the Medicare population and affect quality. This study evaluated the effects of practice-level commercial prices on health care utilization and quality in men with prostate cancer insured by traditional Medicare. From a 20% Medicare sample, the authors identified men with newly diagnosed prostate cancer between 2014-2019 (n=44,653). Using commercial payments from the MarketScan database, they developed a practice-level commercial price index (ratio of commercial prices to Medicare prices). They examined the association of the price index with price standardized spending, overtreatment (treatment among those with >50% noncancer mortality within 10 years), and underuse of diagnostic testing in active surveillance (at least one prostate-specific antigen test and one confirmatory test-MRI, prostate biopsy, genomic test-within 12 months of diagnosis). Practice-level commercial price indices varied from 1.34 (134% of Medicare prices), for practices in the bottom decile, to 3.00, for practices in the top decile. Increasing price index was associated with lower odds of overtreatment (odds ratio, 0.86; 95% confidence interval, 0.76-0.97; p=.01), but not price standardized spending or underuse of diagnostic testing in active surveillance. Commercial prices vary markedly across urology practices. Among newly diagnosed men with traditional Medicare, those managed by practices with higher commercial price indices had lower odds of overtreatment, suggesting improved prostate cancer care quality.

Racial and Ethnic Differences in Prostate Cancer Epidemiology Across Disease States in the VA.

Prostate cancer (PC) care has evolved rapidly as a result of changes in prostate-specific antigen testing, novel imaging, and newer treatments. The impact of these changes on PC epidemiology and racial disparities across disease states remains underexplored. To characterize racial and ethnic differences in the epidemiology of PC states, including nonmetastatic hormone-sensitive PC (nmHSPC), metastatic HSPC (mHSPC), nonmetastatic castration-resistant PC (nmCRPC), and metastatic CRPC (mCRPC). This is a retrospective, population-based cohort study of male US veterans aged 40 years and older with known race and ethnicity and no non-PC malignant neoplasm before study entry receiving care through the Veterans Health Administration. The study period was from 2012 to 2020, with follow-up through 2021. To identify active users, data capture included visits 18 months before and after the study period. Data analysis was performed from March to August 2023. Self-identified race and ethnicity, classified as Black, White, or Hispanic. The primary outcomes were annual age-adjusted incidence rates (IRs) and point prevalence for PC states by race and ethnicity. Trends were evaluated using joinpoint regression. Time to disease progression or death was estimated using nonparametric cumulative incidence. Competing risk models adjusted for age assessed the association of race and ethnicity on disease progression. The study included 6 539 001 veterans (median [IQR] age, 65 [56-74] years), of whom 476 227 had PC (median [IQR] age, 69 [63-75] years). IRs varied by time frame and disease state. Across all states and years, the relative risk among Black vs White patients ranged from 2.09 (95% CI, 2.01-2.18; P < .001) for nmHSPC in 2012 to 4.12 (95% CI, 3.39-5.02; P < .001) for nmCRPC in 2017. In nmHSPC, hazard ratios for progression to mHSPC and nmCRPC were 1.36 (95% CI, 1.33-1.40) and 1.60 (95% CI, 1.51-1.70), respectively, for Black patients and 1.38 (95% CI, 1.31-1.45) and 1.55 (95% CI, 1.40-1.72), respectively, for Hispanic patients vs White patients. In contrast, in mCRPC, the hazard ratio for death was lower for Black (0.84; 95% CI, 0.81-0.88) and Hispanic (0.76; 95% CI, 0.69-0.83) patients compared with White patients. This cohort study of veterans found that Black patients had more than 2-fold higher incidence of all disease states vs White patients. Progression risk was higher for Black and Hispanic patients in early-stage disease, but lower in later disease stages. Despite equal access, Black patients disproportionately experience PC, although progression risks relative to White patients differed according to disease state.

Multidimensional Healthcare Access Barriers to Prostate-Specific Antigen Testing: A Nation-Wide Panel Study in the United States From 2006 to 2020.

Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors. We pooled data from male respondents to Behavior Risk Factor Surveillance Systems (BRFSS) surveys from 2006 to 2020. Questions related to affordability (insurance, cost of visits) and accommodation (regular primary care provider (PCP), physician recommending a PSA test) were considered as individual-level barriers. For availability, we linked provider density from the 2012 Area Health Resource File and estimated driving times to closest health facility within Micropolitan and Metropolitan Statistical Area (MMSA) using Google Earth Engine. These measures were used to compute a spatial accessibility index. We fit survey-weighted, covariate-adjusted logistic regression models to estimate associations of barriers with receipt of PSA within the past 2 years and examined effect modification by sociodemographic factors. There were 185,643 participants, of whom 73% were White, 11% were Black, 4% were Asian, and 11% were Hispanic. Physician recommendation was the strongest predictor of having a PSA test (aOR: 14.5, 95% CI: 13.6, 15.6). Not having a regular PCP (aOR: 0.29, 95% CI: 0.27, 0.31), insurance (aOR: 0.64, 95% CI: 0.58, 0.71), and prohibitive cost of care (aOR: 0.82, 95% CI: 0.75, 0.90) were associated with lower PSA testing. Access barriers were stronger predictors of PSA testing for Asian and White participants compared to other groups (Phet < 0.004 for insurance and regular PCP) and for those with college education compared to those without (Phet < 0.05 for insurance, perceived unaffordability). Physician recommendation was the strongest predictor of receipt of PSA testing, regardless of sociodemographic grouping. Future studies should consider access barriers jointly and across sociodemographic strata.

Prostate-Specific Antigen Stratification for Predicting Advanced Prostate Cancer Events in Men Approaching Age Limits for Recommended Screening.

Our goal was to quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men. We used a random sample of patients in the US Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary end point was time to development of either metastatic prostate cancer or death from prostate cancer. We used cumulative/dynamic modeling to account for competing events (death from non-prostate cancer causes) in studying both the discriminative ability of PSA as well as for positive predictive value and negative predictive value at 3 time points. PSA demonstrated time-dependent predictive discrimination, with receiver operating characteristic area under the curve at 5, 10, and 14 years decreasing from 0.83 to 0.77 to 0.73, respectively, but without statistically significant difference when stratified by race. At PSA thresholds between 1 and 8 ng/mL, the positive predictive value of developing advanced prostate cancer was significantly greater in Black than White patients. For instance, at a PSA > 3, at 5, 10, and 14 years, White patients had 2.4%, 2.9%, and 3.7% risk of an event, whereas Black patients had 4.3%, 6.5%, and 8.3% risk. In men aged 70 to 75 deciding whether to cease PSA testing with borderline-elevated PSA values, the risk of developing metastatic or fatal prostate cancer is quantifiable and relatively low. Risk assessment in this setting must account for the higher incidence of prostate cancer in Black men.

G-Protein-Coupled Receptor-Associated Sorting Protein 1 Overexpression Is Involved in the Progression of Benign Prostatic Hyperplasia, Early-Stage Prostatic Malignant Diseases, and Prostate Cancer.

Background/Objectives: Prostate cancer (PCa) is a prevalent malignancy, necessitating accurate diagnostic methods to distinguish it from benign conditions such as benign prostatic hyperplasia (BPH). Current diagnostic tools, relying primarily on serum prostate-specific antigen (PSA) levels, lack specificity, leading to an over-diagnosis and unnecessary treatment of patients with benign conditions. This study explores G-protein-coupled receptor-associated sorting protein 1 (GASP-1) as a more sensitive biomarker for PCa detection. Methods: Prostate tissue microarrays of healthy, BPH, and prostate cancer patients with different Gleason scores were studied. Polyclonal antibodies targeted against GASP-1 were used for routine immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) analyses. Results: The results indicated a 5-fold difference in serum GASP-1 levels between BPH and PCa, which was validated through GASP-1 IHC. Furthermore, a novel scoring system, the H-score, assesses GASP-1 granules' intensity and size, revealing a clear distinction between BPH and PCa. An additional analysis of GASP-1 expression between PCa cases with different Gleason scores reveals that GASP-1 overexpression correlates with PCa severity, providing insights into disease progression. Conclusions: The study supports GASP-1's role as a promising diagnostic marker, supplementing PSA testing, and offering improved risk stratification for PCa. Additionally, an open-source software system is introduced for an efficient GASP-1 granule color analysis, enhancing diagnostic accuracy.

Prostate-Specific Antigen (PSA) as a Predictor of Prostate Cancer on Transrectal Biopsy: A Meta-Analysis

Prostate cancer is a leading cause of cancer-related death in men globally. Early detection is critical for improving patient outcomes. Prostate-specific antigen (PSA) testing is a widely used screening tool, but its accuracy in predicting prostate cancer on transrectal biopsy remains a topic of debate. This meta-analysis aims to evaluate the diagnostic accuracy of PSA in predicting prostate cancer on transrectal biopsy. A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted to identify relevant studies published between 2013 and 2024. Studies reporting the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of PSA for predicting prostate cancer on transrectal biopsy were included. Data were extracted, and the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated using a random-effects model. Six studies met the inclusion criteria, comprising a total of 1,245 patients. The pooled sensitivity and specificity of PSA for predicting prostate cancer on transrectal biopsy were 0.77 (95% CI, 0.75 - 0.82) and 0.68 (95% CI, 0.62-0.73), respectively. The pooled PLR, NLR, and DOR were 3.27 (95% CI, 2.45-4.37), 0.20 (95% CI, 0.14-0.28), and 16.39 (95% CI, 10.27-26.21), respectively. The pooled AUC was 0.87 (95% CI, 0.84-0.90). In conclusion, PSA demonstrates good diagnostic accuracy in predicting prostate cancer on transrectal biopsy. However, it is essential to consider its limitations, including false positives and negatives. Further research is needed to identify strategies to improve the accuracy of PSA testing and reduce unnecessary biopsies.

Determinants of Prostate Cancer Screening in Korean Men: A Nationwide Study Using the Korean National Cancer Screening Survey 2023.

Research on the prevalence of prostate cancer (PCa) screening and reasons for undergoing screening is limited. We aimed to identify the factors influencing PCa screening behavior and explore the underlying motivations among Korean men. This cross-sectional study used data from the 2023 Korean National Cancer Screening Survey, which employs a nationally representative random sampling method. This study included 1,784 men aged 40-74 years. The respondents reported their experiences with PCa screening. Multivariable logistic regression analysis was conducted to identify the factors associated with participation in PCa screening. The lifetime PCa screening rate was 18.6%. Among screening modalities, transrectal ultrasonography was the most frequently used (31.9%), followed by prostate-specific antigen tests (25.6%) and digital rectal examinations (21.5%). The multivariable analysis identified several factors that significantly increased the likelihood of screening participation, including older age, living with a spouse, poor self-reported health, and abstinence from alcohol consumption in the previous 12 months. Men who had undergone colorectal cancer screening were more likely to participate in PCa screening (adjusted odds ratio, 4.01; 95% confidence interval, 2.03-7.93) than those who had not. The primary motivations for screening were recommendations from family or social networks (31.9%) and inclusion in health examination packages (24.3%), whereas healthcare provider recommendations (18%) and symptomatic concerns (5.7%) were the least influential. Our findings highlight the importance of providing evidence-based information for PCa screening recommendations and the need for improved communication and implementation of a shared decision-making approach for PCa screening in Korea.

Geographical variation in prostate cancer testing explained by socio-economic position in Stockholm

Abstract Background Prostate cancer screening using prostate-specific antigen (PSA) testing is controversial but remains prevalent in many countries. Despite its prevalence there is little information in Sweden or globally on the spatial heterogeneity in PSA testing. This study aims to describe the spatio-temporal variation in PSA testing in the Stockholm region specifically at the municipality and small area level. Additionally, it aims to quantify the extent to which socio-economic position (SEP) indicators such as education, income, and country of birth explain the observed variation in PSA testing. Methods A retrospective population-based register study was conducted, encompassing men aged 40 years and older residing in the Stockholm region from 2007 to 2016. Utilizing spatial smoothing techniques, we calculated the age-standardised proportion of men undergoing PSA testing prior to any prostate cancer diagnosis within each area for every calendar year. Furthermore, we used Bayesian logistic regression models with spatial random effects to estimate the individual-level association between PSA testing and socio-economic position. The proportion of variance in PSA testing explained by various measures of SEP was also estimated at both the municipality and small area levels. Results Significant geographical disparities in PSA testing were observed across small areas within Stockholm. The proportion of variance explained in PSA testing at the small area level was highest for income (32.6%), followed by education (9.7%) and country of birth (7.4%). Incorporating all SEP measures led to a higher proportion of explained variance at the small area level (41.6%) compared to the municipality level (24.8%). Conclusions PSA testing was significantly associated with various socio-economic indicators and some of the spatial variation could be explained by SEP. It would be useful to ascertain whether similar patterns are observed in other regions or countries. Key messages • The findings suggested widespread and consistent opportunistic prostate cancer screening practices within the Stockholm region, raising concerns regarding potential overdiagnosis and overtreatment. • The socio-economic differences in prostate cancer screening could partially explain the differences in cancer incidence and mortality.

Overdiagnosis for screen-detected prostate cancer incorporating patient comorbidities

Abstract Background Evidence regarding the likelihood of overdiagnosis in prostate cancer (CaP) screening with PSA are mainly based on clinical trials, which include younger population with fewer comorbidities than those receiving the test in clinical practice. We aimed to assess the likelihood of overdiagnosis and associated variables using real-world data. Methods Retrospective cohort of men &amp;gt;40 years with PCa, who had been diagnosed being asymptomatic and after a positive PSA test in the previous 12 months in two hospitals (2004-2022). The probability of overdiagnosis was estimated considering the life expectancy of the Spanish male in the year 2022 and the Charlson Comorbidity Index (lead time 10 years). PSA values and Gleason score were included as independent variables. Results Of the 2,331 patients in the cohort, 1,070 (46%) met the inclusion criteria for this analysis. The median follow-up time was 5.7 years (IQR 3.2-8.6). The median age was 71 years (IQR 65-78) and 37% had more than one comorbidity. At diagnosis, the median life expectancy was 12 years (IQR 4-18) and the probability of overdiagnosis was 30.8% (IQR 17.6-52.4). Patients with PSA levels &amp;gt;10 mg/dl tended to be older and with more comorbidities than those with PSA levels 4-10 mg/dl, and thus, with shorter life expectancy. The median probability of overdiagnosis was higher in patients with PSA levels &amp;gt;10 mg/dl (41.4%, IQR 21.5-73.9) than in those with PSA levels 4-10 mg/dl (20.1%, IQR 12.8-30.4), p &amp;lt; 0.001. Correspondingly, patients with Gleason score ≥8 were more likely to be overdiagnosed (median 42.6%, IQR 23.6-68.6) than those with Gleason score ≤6 (median 20.1%, IQR 12.8-30.4) (p &amp;lt; 0.001). Conclusions In clinical practice, older patients with comorbidities showed high PSA levels and Gleason score ≥8, presenting low life expectancy at diagnosis and, therefore, high probability of overdiagnosis. This highlights the importance of considering the patient’s comorbidities when ordering a new PSA test. Key messages • A detailed assessment of the prevalence of comorbidities among CaP patients in real-life settings has significant implications for patient management. • The decision to make an early diagnosis should be based on individual life expectancy, where comorbidity is at least as important as age.

Prostate Specific Antigen (PSA) testing in a general practice 2009-2019.

Prostate-specific antigen (PSA) testing is not recommended as a population screening measure for prostate cancer. PSA testing is nevertheless widespread and is associated with harm due to false-positive test results, overdiagnosis and economic costs. This study sought to document the exposure of patients to PSA testing over a decade in a general medical practice setting. Laboratory results for each year were extracted from the clinical record. A chart review was undertaken for cases of prostate cancer. We report 13,743 PSA results in 3313 men. In any year, 18% of all men and 33% of men aged over 50years had at least one PSA test. Between 4.8 and 21% of first tests exceeded age normal values depending on age. There were 113 incident cancers in the study interval of which 84 (74%) were screen detected. Mortality was lower in screen-detected than symptomatic cancers. Men at our practice are significantly exposed to PSA testing. We found evidence of possible overdiagnosis.

Prostate cancer screening with Prostate-Specific Antigen (PSA) testing: A retrospective study

Objective: To evaluate the results of the prostate-specific antigen (PSA) test used in prostate cancer screening. Methods: This retrospective study was conducted on a total of 1106 male individuals, including 615 people (55.6%) aged 40-54, 379 people (34.3%) aged 55-69, and 112 individuals (10.1%) aged 70 and over. In the study, prostate-specific antigen (PSA) blood test results were performed on a total of 1106 male individuals aged 40 and over registered in the Uludag University Family Health Center, Bursa, Turkey during the 5-years between June 1, 2018, and May 31, 2023, were taken from the database and analyzed. Relationships with sociodemographic characteristics, comorbidities, and risk factors were examined. Data was analyzed using SPSS 25. Results: About 15.5% of the participants were married, 78.4% were single, and 6% were separated from their spouses or widows. The PSA values of the patients referred to the urologist were found to be significantly different between the ages of 55 and 69. It was determined that the PSA levels of the patients with benign prostatic hypertrophy and prostate cancer were higher than the patients without any finding, and the mean was 6.81±4.39 (p=0.01). Conclusion: In our study, it is important to diagnose benign prostatic hypertrophy or prostate cancer in patients aged 55-69 years, whose mean PSA levels were 6.81±4.39, and referred to a urologist. As a contribution to the discussions in the literature, we recommend that the patient with symptoms be referred to the urologist after the test request and the joint decision with the family physician. doi: https://doi.org/10.12669/pjms.40.10.8558 How to cite this: Goktas O. Prostate cancer screening with prostate-specific antigen (PSA) testing: A retrospective study. Pak J Med Sci. 2024;40(10):2324-2330. doi: https://doi.org/10.12669/pjms.40.10.8558 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Factors affecting prostate cancer detection through asymptomatic PSA testing in primary care in England: Evidence from the 2018 National Cancer Diagnosis Audit.

Background Prostate-Specific Antigen (PSA) is used in primary care for prostate cancer detection, either for symptomatic assessment or asymptomatic testing following an informed decision. Aim To estimate the proportion of prostate cancer cases diagnosed following asymptomatic PSA testing, and patient and practice factors influencing this route. Design and setting 2018 English National Cancer Diagnosis Audit (NCDA) data were analysed, with linkage to the national cancer registry, practice-level Quality Outcomes Framework (QOF), and General Practice Patient Survey (GPPS) data. All 2018 NCDA patients with a diagnosis of prostate cancer were included (n = 9,837). Method Patients with recorded biomarker testing and no recorded symptoms prior to diagnosis were classified as asymptomatic PSA detected prostate cancer. Patient (age, ethnicity, deprivation, co-morbidities) and GP practice (geographical location, area deprivation, list size, urgent suspected cancer referral rate, QOF outcomes, GPPS results) factors were analysed for association with asymptomatic PSA testing using mixed effects logistic regression models. Results 1,884 out of 9,837 (19%) prostate cancer cases were detected following asymptomatic PSA testing, 982 (52.1%) of whom were patients aged 50-69 years. Younger age, non-White ethnicity, lower deprivation, and lower co-morbidity count were associated with an increased likelihood of diagnosis following asymptomatic PSA testing. There was a 13-fold variation between practices in the odds of asymptomatic PSA-detected cases, without clear explanatory GP practice-level factors. Conclusion One in five patients with prostate cancer in England are diagnosed after asymptomatic PSA testing in primary care, with large variation in asymptomatic PSA detection between GP practices.

Posttreatment surveillance intensity and overall survival in prostate cancer survivors (AFT-30).

Posttreatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice are lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy or radiation therapy for localized prostate cancer is associated with overall survival. Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent radical prostatectomy or radiation therapy at a Commission on Cancer-accredited facility were randomly sampled. Primary data collected from 10147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of prostate-specific antigen (PSA) tests in the first year after primary treatment (categorized as 0-1 [low intensity], 2 [medium], or ≥3 [high intensity] PSA tests) was associated with overall survival. Secondary outcomes included recurrence-free survival (RFS) and subsequent use of imaging tests, biopsy procedures, and salvage treatment. Median follow-up exceeded 8 years from prostate cancer diagnosis. Overall survival was not statistically significantly different across surveillance intensity groups among radiation therapy (P = .59) or radical prostatectomy (P = .29) patients. RFS was not statistically significantly different across surveillance intensity groups for radiation therapy (P = .13) patients but was for radical prostatectomy (P = .01) patients with high intensity associated with the worst RFS. In both treatments, higher surveillance intensity was associated with more procedures and salvage treatments. In patients with localized prostate cancer, more frequent PSA surveillance testing after radical prostatectomy or radiation therapy was associated with increased procedures and salvage treatments but not overall survival.

The Diagnostic Value of bpMRI in Prostate Cancer: Benefits and Limitations Compared to mpMRI.

Prostate cancer is the second most common cancer in men and a leading cause of death worldwide. Early detection is vital, as it often presents with vague symptoms such as nocturia and poor urinary stream. Diagnostic tools like PSA tests, ultrasound, PET-CT, and mpMRI are essential for prostate cancer management. The PI-RADS system helps assess malignancy risk based on imaging. While mpMRI, which includes T1, T2, DWI, and dynamic contrast-enhanced imaging (DCE), is the standard, bpMRI offers a contrast-free alternative using only T2 and DWI. This reduces costs, acquisition time, and the risk of contrast-related side effects but has limitations in detecting higher-risk PI-RADS 3 and 4 lesions. This study compared bpMRI's diagnostic accuracy to mpMRI, focusing on prostate volume and PI-RADS scoring. Both methods showed strong inter-rater agreement for prostate volume (ICC 0.9963), confirming bpMRI's reliability in this aspect. However, mpMRI detected more complex conditions, such as periprostatic fat infiltration and iliac lymphadenopathy, which bpMRI missed. While bpMRI offers advantages like reduced cost and no contrast use, it is less effective for higher-risk lesions, making mpMRI more comprehensive.

Midlife baseline prostate-specific antigen, velocity, and doubling time association with lethal prostate cancer and mortality.

Midlife baseline prostate-specific antigen (MB PSA), defined as a single PSA value measured between 40-59 years of age, has been proposed as a tool that can limit potential harms of PSA screening. This study aimed to examine the ability of MB PSA versus PSA doubling time (PSADT) and PSA velocity (PSAV) in assessing the likelihood of developing of lethal prostate cancer (PCa) in a diverse and contemporary North American population. Men 40-59 years old, who received their first PSA between the years 1995 and 2019, were included. For MB PSA values, the first PSA test result was included. For PSADT, the first two PSA test results were included. For PSAV, the first three PSA test results within 30 months were included. Selection criteria resulted in a total of 77,594 patients with at least two PSA test results and 11,634 patients with at least three PSA test results. Multivariable Fine-Gray regression was used to examine the impact of the value of the PSA testing methods on the development of lethal PCa (defined as death from PCa or development of metastatic disease either at diagnosis or during follow-up). Time-dependent receiver operating characteristic/area under the curve (AUC) at 5, 10, and 15 years were plotted. In the main cohort, patients were most frequently in the 50-54 age category (32.8%), had a Charlson comorbidity index of 0 (70.5%), and were White (63.2%). Of these, 9.3% had the midlife baseline PSA in the top 10th percentile, and 0.4% had a PSADT 0-6 months. Lethal PCa was diagnosed in 593 (0.8%) patients. The median (interquartile range) time to lethal PCa was 8.6 (3.2-14.9) years. In the main cohort, MB PSA and PSADT showed significant associations with the occurrence of lethal PCa, with a hazard ratio (HR) of 6.10 (95% confidence interval [CI], 4.85-7.68) and HR of 2.20 (95% CI, 1.07-4.54) for patients in the top 10th percentile MB PSA group and in the PSADT between 0 to <6 months group, respectively. In patients with three PSA results available, MB PSA and PSAV showed significant associations with the occurrence of lethal PCa, with a HR of 3.95 (95% CI, 2.29-6.79) and 3.57 (95% CI, 2.17-5.86) for patients in the top 10th percentile MB PSA group and in the in the PSAV >0.4 ng/mL/year group, respectively. PSADT and PSAV did not exhibit higher AUCs than MB PSA in assessing the likelihood of lethal PCa. Specifically, they were 0.818 and 0.708 at 10 and 15 years, respectively, for the PSADT; 0.862 and 0.756 at 10 and 15 years, respectively, for the PSAV; and 0.868 and 0.762 at 10 and 15 years, respectively, for the MB PSA (all p>.05). The study findings are that PSAV or PSADT were not superior to midlife baseline in assessing the likelihood of developing lethal PCa. This suggests that these variables may not have practical use in enhancing PSA screening strategies in a clinical setting.

The impact of non-structured PSA testing on prostate cancer-specific mortality on New Zealand Māori men

ObjectivesTo assess the impact of differences in Prostate-Specific Antigen (PSA) testing rates on prostate cancer (PCa) diagnosis and PCa-specific mortality among Māori men in a New Zealand (NZ) population.Patients and MethodsMāori men aged 40 years or older, without a history of PCa, with a PSA test between 2006 and 2018 were included. The cohort was divided into two groups; the “screened group” (ScG) consisting of men who had at least one PSA test every four years or less, and the “non-screened group” (non-SG). We measured the rate of cancer diagnoses and used competing risk analysis to assess survival.ResultsThe study cohort included 63,939 Māori men, with 37,048 (58%) in the ScG. PCa was more frequently diagnosed in the ScG (3.7% vs. 3.0%, P < 0.001). A higher proportion of high-grade cancers were found in the non-SG (32.7% vs. 25.6%, P = 0.001). The 10-year cancer-specific survival was significantly higher in the ScG (99.4% vs. 98.5%, P < 0.001). In a multivariable risk model, PSA testing frequency was an independent predictor of PCa mortality. (HR 2.43, [95% CI 1.97–3.01], P < 0.001).ConclusionsIn a cohort of only Māori men, lower PSA testing rates were associated with a higher risk of PCa-related death. Therefore, regular PSA testing for Māori could improve cancer-specific survival among Māori men. Regular PSA testing should be considered a priority area for improving PCa survival in this population.