Prostate-specific Antigen Screening Research Articles

Clinical consequences of a genetic predisposition toward higher benign prostate-specific antigen levels

Prostate-specific antigen (PSA) levels are influenced by genetic variation unrelated to prostate cancer risk. Whether a genetic predisposition to a higher PSA level predisposes to a diagnostic work-up for prostate cancer is not known. Participants were 3110 men of African and European ancestries ages 45-70, without prostate cancer and with a baseline PSA < 4ng/mL, undergoing routine clinical PSA screening. The exposure was a polygenic score (PGS) comprising 111 single nucleotide polymorphisms associated with PSA level, but not prostate cancer. We tested whether the PGS was associated with a: 1) PSA value>4ng/mL, 2) International Classification of Diseases (ICD) code for an elevated PSA, 3) encounter with a urologist, or 4) prostate biopsy. Multivariable Cox proportional hazards models were adjusted for age and genetic principal components. Analyses were stratified by age (45-59 years, and 60-70 years old). Association estimates are per standard deviation change in the PGS. The median age was 56.6 years, and 2118 (68%) participants were 45-59 years. The median (IQR) baseline PSA level was 1.0 (0.6-1.7) ng/mL. Among men ages 45-59, the PGS was associated with a PSA > 4 (hazard ratio [HR]=1.35 [95% CI, 1.17-1.57], p=4.5×10-5), an ICD code for elevated PSA (HR=1.30 [1.12-1.52], p=8.0×10-4), a urological evaluation (HR=1.34 [1.14-1.57], p=4.8×10-4), and undergoing a prostate biopsy (HR=1.35 [1.11-1.64], p=0.002). Among men ages 60-70, association effect sizes were smaller and not significant. A predisposition toward higher PSA levels was associated with clinical evaluations of an elevated PSA among men ages 45-59 years. National Institutes of Health (NIH).

Digital Rectal Examination Is Not a Useful Screening Test for Prostate Cancer

BackgroundAnnual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial. ObjectiveTo determine DRE diagnostic performance in a screening trial. Design, setting, and participantsThis analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa. Intervention(1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen–driven biopsies (N = 578). Outcome measurements and statistical analysis(1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome at the time of a prostate biopsy were evaluated. Results and limitations(1) A prospective analysis of 57 men with suspicious DRE at age 45 revealed three PCa. Detection rate by DRE was 0.05% (three of 6537) as compared with a four-fold higher rate by PSA screening (48 of 23 301, 0.21%). The true-positive detection rate by DRE relative to screening by PSA was 0.22 (95% confidence interval [CI] = [0.07–0.72]) and the false-positive detection rate by DRE was 2.2 (95% CI = [1.50–3.17]). (2) Among PSA-screen–detected PCa cases, 86% had unsuspicious DRE (sensitivity relative to PSA was 14%), with the majority of these tumors (86%) located in the potentially accessible zones of the prostate as seen by magnetic resonance imaging. ConclusionsThe performance of stand-alone DRE to screen for PCa is poor. DRE should not be recommended as a PCa screening test in young men. Furthermore, DRE does not improve the detection of PSA-screen–detected PCa. Patient summaryOur report demonstrated the poor diagnostic performance of digital rectal examination in the screening for prostate cancer in young men.

Variation in Receipt of Cancer Screening and Immunizations by 10-year Life Expectancy among U.S. Adults aged 65 or Older in 2019.

The likelihood of benefit from a preventive intervention in an older adult depends on its time-to-benefit and the adult's life expectancy. For example, the time-to-benefit from cancer screening is >10 years, so adults with <10-year life expectancy are unlikely to benefit. To examine receipt of screening for breast, prostate, or colorectal cancer and receipt of immunizations by 10-year life expectancy. Analysis of 2019 National Health Interview Survey. 8,329 non-institutionalized adults >65 years seen by a healthcare professional in the past year, representing 46.9 million US adults. Proportions of breast, prostate, and colorectal cancer screenings, and immunizations, were stratified by 10-year life expectancy, estimated using a validated mortality index. We used logistic regression to examine receipt of cancer screening and immunizations by life expectancy and sociodemographic factors. Overall, 54.7% of participants were female, 41.4% were >75 years, and 76.4% were non-Hispanic White. Overall, 71.5% reported being current with colorectal cancer screening, including 61.4% of those with <10-year life expectancy. Among women, 67.0% reported a screening mammogram in the past 2 years, including 42.8% with <10-year life expectancy. Among men, 56.8% reported prostate specific antigen screening in the past two years, including 48.3% with <10-year life expectancy. Reported receipt of immunizations varied from 72.0% for influenza, 68.8% for pneumococcus, 57.7% for tetanus, and 42.6% for shingles vaccination. Lower life expectancy was associated with decreased likelihood of cancer screening and shingles vaccination but with increased likelihood of pneumococcal vaccination. Despite the long time-to-benefit from cancer screening, in 2019 many US adults age >65 with <10-year life expectancy reported undergoing cancer screening while many did not receive immunizations with a shorter time-to-benefit. Interventions to improve individualization of preventive care based on older adults' life expectancy may improve care of older adults.

Prostate Cancer Screening Uptake in Transgender Females.

Transgender females (TF) can experience aggressive forms of prostate cancer, but their uptake of prostate-specific antigen (PSA) screening for prostate cancer is not well-known. Although national guidelines recommend PSA screening based on age, they do not specify recommendations based on gender identity. We evaluate and compare factors associated with recent PSA screening between cisgender men (CM) and TF using Behavioral Risk Factor Surveillance System (BRFSS) survey data. BRFSS 2018-2020 data was queried to identify CM and TF older than 40 who provided responses to BRFSS questions asking time since last PSA test and whether a provider discussed PSA advantages and disadvantages. Rates of recent screening, defined as receiving a PSA test in the last 2 years with no current or past history of prostate cancer, were calculated for CM and TF. Ages were grouped as younger than 55, 55-69, and 70 years and older based on national PSA screening guidelines, and a 1:4 age-matched cohort between CM and TF was created. Weighted multivariable logistic regressions to measure effects of gender identity, sociodemographic variables, and healthcare access on the odds of recent screening and were calculated and presented as odds ratios (ORs) [95% confidence intervals]. The age-matched cohort had 1,252 CM and 313 TF; TF had a lower overall screening rate than CM (24% vs. 42.3%). TF and CM had similar rates of primary care visits within the last year (85% vs. 86%), but TF were less likely to report that a PSA screen was recommended to them by a provider (33% vs. 49%, p<0.001). Even among all patients with this PSA screening recommendation, fewer TF were recently screened than CM (63% vs. 78%, p = 0.002). In a multivariable regression model, TF had lower odds of recent screening (OR = 0.5 [0.32-0.76], p<0.001) when compared to CM. Discussion of PSA advantages with a provider had higher odds (OR = 15 [10.6-21.5], p<0.001) while discussion of PSA disadvantages was not significantly associated with screening (OR = 0.84 [0.6-1.2], p = 0.3). A college education had higher odds of recent screening (OR = 2.66 [1.2-6.3], p = 0.02) than no high school education. In a multivariable regression model of TF patients, TF aged 70 years and older had higher odds of recent screening (OR = 2.8 [1.1-7.1], p = 0.002) than TF aged 55-69, with screening rates of 14%, 21% and 60% for the under 55, 55-69, and 70+ age groups, respectively. Similarly, to the overall cohort, provider-led discussion of PSA advantages had the strongest association with recent screening (OR = 15.4 [6.15-43.1], p < 0.001), followed by being college educated (OR = 5.7 [1.5-24.9], p = 0.01). TF patients were screened with PSA at a lower rate than CM. Discussing PSA screening benefits with a provider had the largest effect on recent screening among TF patients, highlighting the provider's role in screening uptake. Future studies should continue to evaluate the effects of provider perceptions and barriers to healthcare access on PSA screening in TF.

Utilization of Radical Prostatectomy vs. Radiation Therapy for Gleason Grade Group 5 Prostate Cancer before and after USPSTF Grade D Recommendation against Prostate-Specific Antigen Screening in 2012

The 2012 United States Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen (PSA) screening has resulted in a shift to higher-stage prostate cancer (PC) at diagnosis. While incidence of low-risk prostate cancer has declined, more men are diagnosed with high-risk disease, and multimodal treatment is often required. The impact of this epidemiologic shift on practice patterns, specifically radical prostatectomy (RP) versus definitive radiation therapy (RT), for men with localized PC at high risk of recurrence is unknown. Herein, we evaluate the utilization of RP versus RT in the United States for Gleason grade group 5 (GG5) prostate cancer before and after 2012. We identified 34,011 men with localized GG5 PC treated with (1) RP or (2) RT plus androgen deprivation therapy (ADT) between 2004 and 2017 in the National Cancer Database. We excluded those who were clinically node-positive, had metastatic disease, or received chemotherapy or palliative-intent treatment. Chi-square was used to compare the relative use of RP and RT before versus after January 1, 2012, corresponding to the year of USPSTF recommendation against PSA screening. Annual use of RP versus RT from 2004 to 2017 was compared in academic and non-academic centers using Cochran-Armitage test for trend. Joinpoint regression assessed if 2012 was significant for inflection of crude rates of RP. Finally, we modeled the effect of treatment year (i.e., 2012-2017 versus 2004-2011) on use of RP using multivariable logistic regression. Sensitivity analysis tested an interaction term for facility type (i.e., academic versus community). Tests were two-sided with a 0.05 level of significance. Of the eligible men, 10,745 (31.6%) had T3-T4 disease. Between 2004 and 2011, 36.5% (n = 5,483) underwent RP; between 2012 and 2017, 42.3% (n = 8,034) underwent RP (p = .02). Across all centers, use of RP increased from 31% to 41% (p for trend <.001). In academic centers, use of RP increased from 32% to 44% (p for trend <.001); in community centers, use of RP increased from 30% to 39% (p for trend <.001). 2012 was associated with significant inflection for increase in RP use in all centers. On multivariable analysis, there was an increased odds of receiving RP after 2012 (adjusted OR 1.34, 95% CI 1.28-1.40, p<.001). No differential effect by facility type was observed (p = .15). Utilization of RP for GG5 PC has significantly increased in the United States over the past decade, particularly after the USPSTF Grade D recommendation against PSA screening in 2012. It remains unknown whether oncologic or functional outcomes may be compromised in this group of high-risk men, many of whom require post-prostatectomy RT and/or ADT. While historically rare, prospective comparison of RP versus RT+ADT for GG5 PC may be helpful given the evolving epidemiology of localized PC.

Global viewpoints: updates on prostate cancer in Sub-Saharan Africa.

Prostate cancer (PCa) is a major health concern in Sub-Saharan Africa (SSA), with high incidence and mortality rates. However, the widely used prostate-specific antigen (PSA) screening is not readily available or affordable in SSA. Alternative screening strategies, such as risk stratification approaches and cost-effective PSA tests, are being explored to target high-risk individuals and improve access to screening. Diagnosis of PCa in SSA is challenging due to the lack of access to diagnostic tools and limited healthcare resources. Clinical evaluation and digital rectal examination are commonly used, but PSA testing, magnetic resonance imaging, and biopsy are often limited. As a result, many men in SSA are diagnosed at advanced stages of the disease. Treatment options for PCa in SSA are often limited by a lack of resources and trained healthcare providers. Surgery, radiation therapy, and androgen-deprivation therapy are available but may be inaccessible to many patients. Cultural beliefs and stigma surrounding PCa further impact treatment decisions. Improved patient and community awareness, electronic medical records, and communication between patients and healthcare professionals can enhance evidence-based decision-making and advocate for policy changes. Understanding the genetic determinants and implementing comprehensive strategies can lead to improved outcomes and better control of PCa in SSA.

Low-Value Prostate Cancer Screening Among Young Men With Private Insurance.

No professional society guidelines recommend PSA screening in men younger than age 40; however, data suggest testing occurs at meaningful rates in this age group. The purpose of this study was to identify the rate of PSA testing in men under 40. This is a population-based, retrospective cohort study from 2008 to 2017. Using the MarketScan database, rates of testing for the sum of the annual population of men at risk were evaluated. Descriptive statistics and statistical analyses were performed in men continuously enrolled in the database for at least 5 year. Results were stratified by receipt of PSA testing and by age group. The association of diagnoses and Charlson Comorbidity Index with receipt of PSA test was evaluated using multivariable logistic regression models. We identified 3,230,748 men ages 18 to 39 who were enrolled for at least 5 years. The rate of ever receiving PSA testing was 0.6%, 1.7%, 8.5%, and 9.1% in men less than 25, 25 to 29, 30 to 34, and 35 to 39 years, respectively. Multivariable logistic regression showed that relative to all men 18 to 39, patients who received PSA testing had higher odds of a diagnosis of hypogonadism (OR 11.77) or lower urinary tract symptoms (OR 4.19). This study found a remarkable number of young men receive PSA testing, with a strong association with diagnoses of lower urinary tract symptoms and hypogonadism. Clinicians need to be educated that assessment and management guidelines for other urologic diagnoses now defer PSA testing to prostate cancer screening guidelines.

Do Swiss urologists and Swiss internists screen themselves and their relatives for prostate cancer? A questionnaire study.

Prostate-specific antigen (PSA) screening for men at risk of prostate cancer is controversial. The current recommendation is to raise awareness of prostate cancer and offer PSA screening in accordance with shared decision- making. Whether the possibility of a PSA screen is discussed with the patient depends on the treating physician, but data on physicians' attitudes towards PSA screening are scarce. This study aimed to examine internists' and urologists' personal PSA screening activity as an indicator of their attitude towards PSA screening. Members of the Swiss Society of Urology and the Swiss Society of General Internal Medicine were asked in 08/2020 to anonymously complete an online survey about personal PSA screening behaviour for themselves, their fathers, brothers and partners. Categorical and continuous variables were compared by chi-squared tests and t-tests, respectively. In total, 190/295 (response rate: 64%) urologists and 893/7400 (response rate: 12%) internists participated in the survey. Of the participants, 297/1083 (27.4%) were female. Male urologists >50 years of age screened themselves more often than male internists >50 years of age (89% vs 70%, p <0.05). Furthermore, urologists reported recommending screening statistically significantly more often than internists to their brother, father or partner regardless of their sex (men: 38.1% vs 18.5%; p <0.05; women: 81.8% vs 32.2%; p <0.05). CONCLUSIONS: Most participating male physicians >50 years of age have screened themselves for prostate cancer. Furthermore, PSA screening of relatives was significantly associated with the urology specialty. The reasons physicians screen themselves substantially more often than the public and why male and female urologists as well as male internists perform PSA screening more frequently in their private environment than female internists should be further examined.

Differentiation of patients with and without prostate cancer using urine 1 H NMR metabolomics.

Prostate cancer (PCa) is one of the most prevalent cancers in men worldwide. For its detection, serum prostate-specific antigen (PSA) screening is commonly used, despite its lack of specificity, high false positive rate, and inability to discriminate indolent from aggressive PCa. Following increases in serum PSA levels, clinicians often conduct prostate biopsies with or without advanced imaging. Nuclear magnetic resonance (NMR)-based metabolomics has proven to be promising for advancing early-detection and elucidation of disease progression, through the discovery and characterization of novel biomarkers. This retrospective study of urine-NMR samples, from prostate biopsy patients with and without PCa, identified several metabolites involved in energy metabolism, amino acid metabolism, and the hippuric acid pathway. Of note, lactate and hippurate-key metabolites involved in cellular proliferation and microbiome effects, respectively-were significantly altered, unveiling widespread metabolomic modifications associated with PCa development. These findings support urine metabolomics profiling as a promising strategy to identify new clinical biomarkers for PCa detection and diagnosis.

Racial Disparities in Prostate Cancer Screening: The Role of Shared Decision Making

The 2018 U.S. Preventive Services Task Force recommendations endorsed shared decision making for men aged 55-69 years, encouraging consideration of patient race/ethnicity for prostate-specific antigen screening. This study aimed to assess whether a proxy shared decision-making variable modified the impact of race/ethnicity on the likelihood of prostate-specific antigen screening. A cross-sectional analysis of men aged between 55 and 69 years, who responded to the prostate-specific antigen screening portions of the 2020 U.S.-based Behavioral Risk Factor Surveillance System survey, was performed between September and December 2022. Complex sample multivariable logistic regression models with an interaction term combining race and estimated shared decision making were used to test whether shared decision making modified the impact of race/ethnicity on screening. Of a weighted sample of 26.8 million men eligible for prostate-specific antigen screening, 25.7% (6.9 million) reported for prostate-specific antigen screening. In adjusted analysis, estimated shared decision making was a significant predictor of prostate-specific antigen screening (AOR=2.65, 95% CI=2.36, 2.98, p<0.001). The interaction between race/ethnicity and estimated shared decision making on the receipt of prostate-specific antigen screening was significant (pint=0.001). Among those who did not report estimated shared decision making, both non-Hispanic Black (OR=0.77, 95% CI=0.61, 0.97, p=0.026) and Hispanic (OR=0.51, 95% CI=0.39, 0.68, p<0.001) men were significantly less likely to undergo prostate-specific antigen screening than non-Hispanic White men. On the contrary, among respondents who reported estimated shared decision making, no race-based differences in prostate-specific antigen screening were found. Although much disparities research focuses on race-based differences in prostate-specific antigen screening, research on strategies to mitigate these disparities is needed. Shared decision making might attenuate the impact of race/ethnic disparities on the likelihood of prostate-specific antigen screening.

Prevalence of MRI lesions in men responding to a GP-led invitation for a prostate health check: a prospective cohort study

ObjectiveIn men with a raised prostate-specific antigen (PSA), MRI increases the detection of clinically significant cancer and reduces overdiagnosis, with fewer biopsies. MRI as a screening tool has not been...

Risk-stratified multi-round PSA screening for prostate cancer integrating the screening reference level and subgroup-specific progression indicators

BackgroundAlthough prostate-specific antigen (PSA) is widely used in prostate cancer (PCa) screening, nearly half of PCa cases are missed and less than one-third of cases are non-lethal. Adopting diagnostic criteria in population-based screening and ignoring PSA progression are presumed leading causes.MethodsA total of 31,942 participants with multi-round PSA tests from the PLCO trial were included. Time-dependent receiver-operating-characteristic curves and area under curves (tdAUCs) were performed to determine the screening reference level and the optimal subgroup-specific progression indicator. Effects of risk-stratified multi-round PSA screening were evaluated with multivariable Cox regression and measured with hazard ratio [HR (95%CIs)].ResultsAfter a median follow-up of 11.6 years, a total of 3484 PCa cases and 216 PCa deaths were documented. The tdAUC of 10-year incidence PCa with PSA was 0.816, and the cut-off value was 1.61 ng/ml. Compared to subgroup with stable negative PSA in both first-round (FR) and last-round (LR) tests [FR(−)/LR(−)], HRs (95%CI) of PCa incidence were 1.66 (1.20–2.29), 8.29 (7.25–9.48), and 14.52 (12.95–16.28) for subgroups with loss of positive PSA[FR(+)/LR(−)], gain of positive PSA[FR(−)/LR(+)], and stable positive PSA[FR(+)/LR(+)]; while HRs(95%CI) of PCa mortality were 1.47 (0.52–4.15), 5.71 (3.68–8.86), and 5.01 (3.41–7.37). After excluding regressive PSA [(namely FR(+)/LR(−)], absolute velocity was the shared optimal progression indicator for subgroups with FR(−)/LR(−), FR(−)/LR(+), and FR(+)/LR(+), with tdAUCs of 0.665, 0.681 and 0.741, and cut-off values of 0.07, 0.21, and 0.33 ng/ml/year. After reclassifying participants into groups with positive and negative progression based on subgroup-specific progression indicators, incidence HR (95%CI) were 2.41 (1.87–3.10), 2.91 (2.43–3.48), and 3.16 (2.88–3.46) for positive progression compared to negative progression within subgroups of FR(−)/LR(−), FR(−)/LR(+), and FR(+)/LR(+), while mortality HR (95%CI) were 2.22 (0.91–5.38), 2.37 (1.28–4.38), and 2.98 (1.94–4.59). To improve screening performances by excluding regressive PSA and low-risk positive progression in FR(−)/LR(−), optimized screening strategy not only significantly reduce 32.4% of missed PCa (54.0% [1881/3484] vs. 21.6% [754/3484], P < 0.001), but also detected additional 8.0% of high-grade PCa (Gleason score 7–10: 36.0% [665/1849] vs. 28.0% [206/736], P < 0.001) than traditional screening strategy.ConclusionsRisk-stratified multi-round PSA screening strategy integrating the screening reference level and the optimal subgroup-specific progression indicator of PSA could be recommended as a fundamental strategy to reduce missed diagnosis and improve the detection of high-grade PCa cases.

Changes in Prostate-specific Antigen Screening after the 2018 United States Preventive Services Task Force Recommendations and Through the COVID-19 Pandemic

We analyzed trends in prostate-specific antigen (PSA) screening for prostate cancer, with a focus on the impact of the 2018 US Preventive Services Task Force (USPSTF) recommendations and the COVID-19 outbreak. Using National Health Interview Survey data, we performed difference-in-difference (DID) analyses to examine the PSA screening trend for men aged 55–69 yr, the target population in the 2018 USPSTF update, with men aged >69 yr included as the reference and adjustment for sociodemographic factors. We found that PSA screening increased for men aged 55–69 yr (+4.6%, 95% confidence interval [CI] 1.7–7.5%) or >69 yr (+6.5%, 95% CI 2.7–10.4%) in 2019 (after the 2018 recommendations) in comparison to 2015. There was a decrease in PSA screening for men aged 55–69 yr in 2021 in comparison to 2019 (after the COVID-19 outbreak in 2020) of −3.1% (95%CI −0.4% to −5.8%). Adjusted DID analysis revealed no significant variations in the rate of change in PSA screening between the two age groups following both events. Despite its observational nature, our design mitigates major challenges in inferring causal relationships. Our results suggest a causal relationship between the 2018 screening guidelines and an increase in screening rates for men aged 55–69 yr. Conversely, they also indicate that preventive care disruptions related to COVID-19 may have induced deceleration or potentially reversal of these advances. Patient summaryWe used data from a large national survey to study the rate of prostate-specific antigen (PSA) screening for prostate cancer in the USA in response to the 2018 United States Preventive Services Task Force recommendations and to the COVID-19 pandemic. We found an increase in PSA screening in 2019 among men aged 55–69 yr, the target population in the 2018 recommendations, as well as men aged >69 yr. However, this increase was reduced after the COVID-19 outbreak. It remains to be seen how PSA screening continues to change as the world recovers from COVID-19.

PROSTATE CANCER SCREENING USING THE PROSTATE-SPECIFIC ANTIGEN (PSA) TEST

We aimed to conduct a systematic review and meta-analysis on published literature extracted from PubMed/Medline, Google scholar, and Cochrane library. The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, over diagnosis, and costs.

Temporal and Racial Trends in Prostate Specific Antigen Screening for US Men With Family History of Prostate Cancer.

Limited data exists on trends in prostate-specific antigen (PSA) screening in men with family history of prostate cancer (PCa). 1) to study age-stratified temporal trends in PSA screening from 2000-2018 for men with a family history of PCa and black men with family history of PCa; and 2) identify determinants associated with receipt of PSA screening in aforementioned groups. We identified men aged ≥40 without prior history of PCa using data from National Health Institution Survey (NHIS) 2000-2018 who self-reported PSA testing in the last 12 months. Age-stratified temporal trends and weighted multivariable logistic regression analyses were assessed. PSA screening increased for men with a family history of prostate cancer between NHIS 2000 (28.9%) and 2005 (41.9%), with stable rates for the following years. Black men with family history of PCa showed no significant change in PSA screening rates regardless of age. Controlling for socio-demographics and access to healthcare provider, younger age (40-54) and later survey years (2013-2018) were associated with a lower likelihood of PSA screening overall and for black men, but not for those with positive family history. Data from nationally representative study of US men indicated that the annual PSA screening rates for men with a family history of PCa was higher than reported for the overall male population. We believe this represents the first study on trends and determinants of PSA screening in US men with a family history of PCa.

Association of cigarette smoking habits with the risk of prostate cancer: a systematic review and meta-analysis

BackgroundAssociation of cigarette smoking habits with the risk of prostate cancer is still a matter of debate. This systematic review and meta-analysis aimed to assess the association between cigarette smoking and prostate cancer risk.MethodsWe conducted a systematic search on PubMed, Embase, Cochrane Library, and Web of Science without language or time restrictions on June 11, 2022. Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective cohort studies that assessed the association between cigarette smoking habits and the risk of prostate cancer were included. Quality assessment was conducted using the Newcastle–Ottawa Scale. We used random-effects models to obtain pooled estimates and the corresponding 95% confidence intervals.ResultsA total of 7296 publications were screened, of which 44 cohort studies were identified for qualitative analysis; 39 articles comprising 3 296 398 participants and 130 924 cases were selected for further meta-analysis. Current smoking had a significantly reduced risk of prostate cancer (RR, 0.74; 95% CI, 0.68–0.80; P < 0.001), especially in studies completed in the prostate-specific antigen screening era. Compared to former smokers, current smokers had a significant lower risk of PCa (RR, 0.70; 95% CI, 0.65–0.75; P < 0.001). Ever smoking showed no association with prostate cancer risk in overall analyses (RR, 0.96; 95% CI, 0.93–1.00; P = 0.074), but an increased risk of prostate cancer in the pre-prostate-specific antigen screening era (RR, 1.05; 95% CI, 1.00–1.10; P = 0.046) and a lower risk of prostate cancer in the prostate-specific antigen screening era (RR, 0.95; 95% CI, 0.91–0.99; P = 0.011) were observed. Former smoking did not show any association with the risk of prostate cancer.ConclusionsThe findings suggest that the lower risk of prostate cancer in smokers can probably be attributed to their poor adherence to cancer screening and the occurrence of deadly smoking-related diseases, and we should take measures to help smokers to be more compliant with early cancer screening and to quit smoking.Trial registrationThis study was registered on PROSPERO (CRD42022326464).

Impact of PSA testing on secondary care costs in England and Wales: estimates from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

BackgroundScreening men for prostate cancer using prostate-specific antigen (PSA) testing remains controversial. We aimed to estimate the likely budgetary impact on secondary care in England and Wales to inform screening decision makers.MethodsThe Cluster randomised triAl of PSA testing for Prostate cancer study (CAP) compared a single invitation to men aged 50–69 for a PSA test with usual care (no screening). Routinely collected hospital care data were obtained for all men in CAP, and NHS reference costs were mapped to each event via Healthcare Resource Group (HRG) codes. Secondary-care costs per man per year were calculated, and cost differences (and population-level estimates) between arms were derived annually for the first five years following randomisation.ResultsIn the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million.ConclusionsIntroducing a single PSA screening test for men aged 50–69 across England and Wales could lead to very high initial secondary-care costs.

HSD105 Sociodemographic Variations in PSA Screening Use: A Cross-Sectional Analysis of Data from the National Health Interview Survey

To assess sociodemographic variations in prostate specific antigen (PSA) screening outside the U.S. Preventive Services Task Force (USPSTF) recommended age range.

Prospective Validation Study of a Novel Integrated Pathway Based on Clinical Features, Magnetic Resonance Imaging Biomarkers, and MicroRNAs for Early Detection of Prostate Cancer

BackgroundProstate cancer (PCa) is the most diagnosed cancer in men, with an increasing need to integrate noninvasive imaging and circulating microRNAs beyond prostate-specific antigen for screening and early detection. ObjectiveTo validate magnetic resonance imaging (MRI) biomarkers and circulating microRNAs as triage tests for patients directed to prostate biopsy, and to test different diagnostic pathways to compare their performance on patients’ outcome, in terms of unnecessary biopsy avoidance. Design, setting, and participantsA prospective single-center cohort study, enrolling patients with PCa suspicion who underwent MRI, MRI-directed fusion biopsy (MRDB), and circulating microRNAs, was conducted. A network-based analysis was used to identify MRI biomarkers and microRNA drivers of clinically significant PCa. InterventionMRI, MRDB, and blood sampling. Outcome measurements and statistical analysisThe decision curve analysis was exploited to assess the performance of the proposed diagnostic pathways and to quantify their benefit in terms of biopsy avoidance. Results and limitationsOverall, 261 men were enrolled and underwent MRDB for PCa detection. A total of 178 patients represented the entire cohort: 55 (30.9%) were negative for PCa, 39 (21.9%) had grade group (GG) 1 PCa, and 84 (47.2%) had GG >1 PCa. The proposed integrated pathway, including clinical data, MRI biomarkers, and microRNAs, provided the best net benefit with a biopsy avoidance rate of about 20% at a low disease probability. The main limitation is the monocentric design in a referral center. ConclusionsThe integrated pathway represents a validated model that sees MRI biomarkers and microRNAs as a prebiopsy triage of patients at a risk for clinically significant PCa. The proposed pathway showed the highest net benefit in terms of unnecessary biopsy avoidance. Patient summaryThe proposed integrated pathway for early detection of prostate cancer (PCa) allows accurate patient allocation to biopsy and patients’ stratification into risk group categories, reducing overdiagnosis and overtreatment of clinically insignificant PCa.

Genetically adjusted PSA levels for prostate cancer screening

Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10−8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGSPSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P = 6.2 × 10−14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10−12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P = 7.2 × 10−4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.