Antigen Based Prostate Cancer Screening Research Articles

Prostate-Specific Antigen-Based Prostate Cancer Screening: One for All or Individualized for Each Race? – A Narrative Review

Prostate cancer (PCa) is the second most common cancer globally. However, significant disparities in incidence and mortality exist between countries, especially between Western and Asian regions. This review discusses the applicability of Western-based randomized controlled trials on prostate-specific antigen-based PCa screening in other regions such as Korea, where PCa is less frequently diagnosed but tends to present more aggressive features compared to Western countries. The paper also reviews major guidelines and landmark trials, emphasizing the importance of an individualized approach in the context of regional diversity in PCa incidence and mortality.

What is cancer? A focus on Grade Group 1 prostate cancer.

Since the widespread adoption of prostate-specific antigen-based screening for prostate cancer, the prevalence of Grade Group 1 (GG1) prostate cancer has risen. Historically, these patients were subjected to overtreatment of this otherwise indolent disease process, leading to significant quality-of-life detriments. Active surveillance as a primary management strategy has allowed for a focus on early detection while minimising morbidity from unnecessary intervention. Here we provide a comprehensive overview of the characteristics of GG1 prostatic adenocarcinoma, including its histological features, genomic differentiators, clinical progression, and implications for treatment guidelines, all supporting the movement to reclassify GG1 disease as a non-cancerous entity.

Disease-related complications in patients with metastatic hormone-sensitive prostate cancer.

Prostate-specific antigen-based screening for prostate cancer reportedly does not improve cancer-specific survival. However, there remain concerns about the increasing incidence of advanced disease at initial presentation. Here, we investigated the incidences and types of complications that occur during the course of disease in patients with metastatic hormone-sensitive prostate cancer (mHSPC). This study included 100 consecutive patients who were diagnosed with mHSPC at five hospitals from January 2016 to August 2017. Analyses were conducted using patient data extracted from a prospectively collected database, along with information about complications and readmission obtained from electronic medical records. The median patient age was 74 years and the median serum prostate-specific antigen level at diagnosis was 202.5 ng/mL. Ninety-nine patients received androgen deprivation therapy; 17 of these patients also received chemotherapy. During a mean follow-up period of 32.9 months, 41 patients reported bone pain; of these patients, 21 developed pathologic fractures and eight had cord compression. Twenty-eight patients developed retention of urine; of these patients, 10 (36%) required surgery and 11 (39%) required long-term urethral catheter use. Among 15 patients who developed ureteral obstruction, four (27%) required ureteral stenting and four (27%) required long-term nephrostomy drainage. Other complications included anaemia (41%) and deep vein thrombosis (4%). Fifty-nine (59%) patients had ≥1 unplanned hospital admission during the course of disease; 16% of such patients had >5 episodes of readmission. Among patients with mHSPC, 70% experienced disease-related complications and unplanned hospital admissions, which substantially burdened both patients and the healthcare system.

A Detailed Evaluation of the Effect of Prostate-specific Antigen–based Screening on Morbidity and Mortality of Prostate Cancer: 21-year Follow-up Results of the Rotterdam Section of the European Randomised Study of Screening for Prostate Cancer

BackgroundConsidering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial. ObjectiveTo provide an update on the effect of prostate-specific antigen (PSA)-based screening on PCa-specific mortality (PCSM), metastatic disease, and overdiagnosis in the Dutch arm of the ERSPC. Design, setting, and participantsBetween 1993 and 2000, a total of 42376 men, aged 55–74 yr, were randomised to a screening or a control arm. The main analysis was performed with men aged 55–69 yr (n = 34831). Men in the screening arm were offered PSA-based screening with an interval of 4 yr. Outcome measurements and statistical analysisIntention-to-screen analyses with Poisson regression were used to calculate rate ratios (RRs) of PCSM and metastatic PCa. Results and limitationsAfter a median follow-up of 21 yr, the RR of PCSM was 0.73 (95% confidence interval [CI]: 0.61–0.88) favouring screening. The numbers of men needed to invite (NNI) and needed to diagnose (NND) to prevent one PCa death were 246 and 14, respectively. For metastatic PCa, the RR was 0.67 (95% CI: 0.58–0.78) favouring screening. The NNI and NND to prevent one metastasis were 121 and 7, respectively. No statistical difference in PCSM (RR of 1.18 [95% CI: 0.87–1.62]) was observed in men aged ≥70 yr at the time of randomisation. In the screening arm, higher rates of PCSM and metastatic disease were observed in men who were screened only once and in a selected group of men above the screening age cut-off of 74 yr. ConclusionsThe current analysis illustrates that with a follow-up of 21 yr, both absolute metastasis and mortality reduction continue to increase, resulting in a more favourable harm-benefit ratio than demonstrated previously. These data do not support starting screening at the age of 70–74 yr and show that repeated screening is essential. Patient summaryProstate-specific antigen–based prostate cancer screening reduces metastasis and mortality. Longer follow-up shows fewer invitations and diagnoses needed to prevent one death, a positive note towards the issue of overdiagnosis.

Abrogation of survival disparity between insured and uninsured individuals after the USPSTF's 2012 prostate-specific antigen-based prostate cancer screening recommendation.

77 Background: In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. Studies have found that insured patients with prostate cancer have better outcomes than uninsured patients. We examined the recommendation’s effects on survival disparities based on insurance status as well as socioeconomic quintile, marital status, and housing (urban/rural). Methods: Using the SEER18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and one of four factors: insurance status, socioeconomic quintile, marital status, and housing (urban/rural). The SEER-designated socioeconomic quintile was based on variables including median household income and education index. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010-2012 or post-USPSTF era if diagnosed in 2014-2016. Disparities were measured with the Cox proportional hazards model. Results: We identified 282,994 patients diagnosed with prostate cancer. During the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.29, 95% CI 1.06-1.58, p = 0.01). This survival disparity narrowed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients. Moreover, the survival disparity was no longer observed during the post-USPSTF era (aHR 0.91, 95% CI 0.61-1.38, p = 0.67). The survival disparity based on socioeconomic quintile also narrowed but remained significant. In contrast, the survival disparity based on marital status widened, while housing status was not associated with survival disparities in either era. Conclusions: From the pre- to the post-USPSTF era, insured patients with prostate cancer observed a significant decrease in survival that made their survival outcomes similar to that of uninsured patients. Although the underlying reasons are not clear, the USPSTF’s 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without improving the survival of uninsured patients.[Table: see text]

Tumour markers in prostate cancer: The post-prostate-specific antigen era.

Although prostate-specific antigen-based prostate cancer screening had a positive impact in reducing prostate cancer mortality, it also led to overdiagnosis, overtreatment and a significant number of unnecessary biopsies. In the post-prostate-specific antigen era, new biomarkers have emerged that can complement the information given by prostate-specific antigen, towards a better cancer diagnostic specificity, and also allowing a better estimate of the aggressiveness of the disease and its clinical outcome. That means those markers have the potential to assist the clinician in the decision-making processes, such as whether or not to perform a biopsy, and to make the best treatment choice among the new therapeutic options available, including active surveillance in lower risk disease. In this article, we will review several of those more recent diagnostic markers (4Kscore®, [-2]proPSA and Prostate Health Index, SelectMDx®, ConfirmMDx®, Progensa® Prostate Cancer Antigen 3, Mi-Prostate Score, ExoDx™ Prostate Test, the Stockholm3 test and ERSPC risk calculators) and prognostic markers (OncotypeDX® Genomic Prostate Score, Prolaris®, Decipher® and ProMark®). We will also address some new liquid biopsy approaches - circulating tumour cells and cell-free DNA - with a potential role in metastatic castration-resistant prostate cancer and will briefly give some future perspectives, mostly outlooking epigenetic markers.

Abrogation of survival disparity between Black and White individuals after the USPSTF's 2012 prostate-specific antigen-based prostate cancer screening recommendation.

In May 2012, the US Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer (PCa), assigning it a grade D. This decision then was modified in 2018 to a grade C for men aged 55 to 69 years. The authors hypothesized that changes in screening practices would reduce survival outcomes for both Black and White men but maintain racial discrepancies in outcomes. Using the Surveillance, Epidemiology, and End Results database, the authors examined PCa-specific survival based on race and year of diagnosis. The period between January 2010 and December 2012 was categorized as the pre-USPSTF era, whereas the period between January 2014 and December 2016 was classified as the post-USPSTF era. The year 2013 was considered the transition year and was excluded from the analysis. A total of 49,388 men were identified in the pre-USPSTF era who were diagnosed with PCa, approximately 83.7% of whom were White and 16.3% of whom were Black. In the post-USPSTF era, a total of 41,829 men were diagnosed with PCa, approximately 82.7% of whom were White and 17.3% of whom were Black. When compared with the pre-USPSTF era, men diagnosed in the post-USPSTF era were found to have more adverse clinical features. In the pre-USPSTF era, White men were less likely to die of PCa than Black men. This survival disparity between White and Black men was no longer observed in the post-USPSTF era. In men diagnosed with PCa between 2014 and 2016, a survival disparity between White and Black men was not observed due to a decrease in survival among White men while the survival of Black men remained steady.

Shared decision making and prostate-specific antigen based prostate cancer screening following the 2018 update of USPSTF screening guideline.

Previous study reported shared decision making was underused in PSA-based prostate cancer screening. In mid-2018, the US Preventive Service Task Force recommended shared decision making (SDM) before PSA-based prostate cancer screening among men aged 55-69 year while remained against PSA testing in men aged 70 or older. The objective of this study is to examine recent changes in SDM and prostate cancer screening following recent USPSTF recommendations. A retrospective cross-sectional study among men aged 50 years or older were conducted using 2015 and 2018 National Health Interview Survey data (n = 10,926). Outcomes included self-reported PSA testing for prostate cancer screening last year, and if yes, whether respondent ever had a discussion with the healthcare provider about its advantages and disadvantages. Analyses were stratified by respondent's age (50-54 vs. 55-69 vs. 70+). Routine PSA screening rates remained stable from 34.3% in 2015 to 35.4% in first half of 2018, and 36.0% in second half of 2018 (p trend = 0.57). A similar pattern was found in men ≥70 years (p trend = 0.98). Receipt of SDM increased in men aged ≥50 years from 30.5% in 2015 to 33.6% in first half of 2018, and 36.7% in second half of 2018 (p trend = 0.002). The increase was most prominent in men aged 55 to 69 years (31.6, 36.9, and 40.2% in 2015, first half of 2018 and second half of 2018 respectively; p trend = 0.001). Between 2015 and 2018, there was no significant increase in the PSA-based prostate cancer screening. However, a significant increasing trend in SDM was observed, especially in men aged 55-69 years.

Factors Related to Prostate-Specific Antigen-Based Prostate Cancer Screening in Primary Care: Retrospective Cohort Study of 120,587 French Men Over the Age of 50 Years.

BackgroundInternational guidelines recommend avoiding prostate-specific antigen (PSA)-based prostate cancer screening in the elderly when life expectancy is less than 10 years. For younger men, most recommendations encourage a shared decision-making process taking into account patient comorbidities.ObjectiveThe objective was to assess the performance of PSA-based prostate cancer screening in men older than 74 years and assess whether the presence (vs absence) of comorbidities was related to the performance of PSA testing in younger men aged 50 to 74 years who were eligible for screening.MethodsWe analyzed data from the French national health care database (Loire-Atlantique geographic area). We reported the follow-up of two cohorts of men from April 1, 2014, to March 31, 2016: 22,480 men aged over 74 years and 98,107 men aged 50 to 74 years. We analyzed whether these patients underwent PSA testing after 2 years of follow-up and whether PSA testing performance was related to the following patient-related variables: age, low income, proxy measures indicative of major comorbidities (repeated ambulance transportation, having one of 30 chronic diseases, taking 5 or more drugs per day), or proxy measures indicative of specific comorbidities (cancer diseases, cardiovascular diseases, or psychiatric disorders). Statistical analysis was based on a multivariate mixed-effects logistic regression.ResultsThe proportion of patients who underwent a PSA-based screening test was 41.35% (9296/22,480) among men older than 74 years versus 41.05% (40,275/98,107) among men aged 50 to 74 years. The following factors were associated with less frequent PSA testing in men older than 74 years—age (odds ratio [OR] 0.89, 95% CI 0.88-0.89), low income (OR 0.18, 95% CI 0.05-0.69), suffering from a chronic disease (OR 0.82, 95% CI 0.76-0.88), repeated ambulance transportation (OR 0.37, 95% CI 0.31-0.44), diabetes requiring insulin (OR 0.51, 95% CI 0.43-0.60), dementia (OR 0.68, 95% CI 0.55-0.84), and antipsychotic treatment (OR 0.62, 95% CI 0.51-0.75)—whereas cardiovascular drug treatment was associated with more frequent PSA testing (OR 1.6, 95% CI 1.53-1.84). The following factors were associated with less frequent PSA testing in men aged 50 to 74 years—low income (OR 0.61, 95% CI 0.55-0.68); nonspecific conditions related to frailty: suffering from a chronic disease (OR 0.80, 95% CI 0.76-0.83), repeated ambulance transportation (OR 0.29, 95% CI 0.23-0.38), or chronic treatment with 5 or more drugs (OR 0.89, 95% CI 0.83-0.96); and various specific comorbidities: anticancer drug treatment (OR 0.67, 95% CI 0.55-0.83), diabetes requiring insulin (OR 0.55, 95% CI 0.49-0.61), and antiaggregant treatment (OR 0.91, 95% CI 0.86-0.96)—whereas older age (OR 1.07, 95% CI 1.07-1.08) and treatment with other cardiovascular drugs (OR 2.23, 95% CI 2.15-2.32) were associated with more frequent PSA testing.ConclusionsIn this study, 41.35% (9296/22,480) of French men older than 74 years had a PSA-based screening test. Although it depends on patient comorbidities, PSA testing remains inappropriate in certain populations.

Factors Influencing Prostate Specific Antigen Testing in the United States

IntroductionGiven the ongoing controversies regarding its benefit, prostate specific antigen based prostate cancer screening should be offered with patient preferences in mind. Understanding subsets of men who may or may not choose prostate specific antigen screening and their associated characteristics may allow more efficient care and may identify subsets of patients for whom additional counseling is warranted. MethodsWe analyzed male participants from the 2001 to 2010 cycles of the NHANES (National Health and Nutrition Examination Survey) who were 40 years old or older, and without a history of prostate cancer, recent prostate manipulation or hormone therapy use (8,133). All men were given an opportunity to undergo or refuse prostate specific antigen testing after a standardized explanation about prostate cancer screening from a physician. Univariable and multivariable logistic regressions were conducted after adjusting for survey weights to identify independent sociodemographic and clinical predictors for opting out of prostate specific antigen testing. ResultsA total of 7,732 men met the inclusion criteria. Overall 95.64% of the study cohort elected to undergo prostate specific antigen testing. The odds of declining prostate specific antigen testing were significantly higher in men 80 years old or older (OR 1.78, p=0.008), black men (OR 3.23, p <0.001), divorced/separated men (OR 1.66, p=0.002) and men with a preexisting nonprostate malignancy (OR 1.65, p=0.012). ConclusionsIn the setting of the NHANES program, between 2001 and 2010 the majority of men who were offered prostate cancer screening underwent prostate specific antigen testing. Black men, a subgroup subject to more aggressive prostate cancer, were more likely to refuse prostate specific antigen testing.

Patterns of Prostate-Specific Antigen Test Use in the U.S., 2005–2015

Recommendations for prostate-specific antigen-based screening for prostate cancer are placing increasing emphasis on men aged 55-69 years. The goal of the current study is to describe patterns of population-based prostate-specific antigen testing with details about that age group. National Health Interview Surveys from 2005 to 2015 were analyzed in 2017 to estimate routine prostate-specific antigen testing in the past year from self-reported data by age group (40-54, 55-69, ≥70 years), and also by risk group, defined as African American men or men with a family history of prostate cancer versus other men. Differences between successive survey years by age and risk groups were assessed by predicted margins and rate ratios with 99% CIs, using logistic regressions. Prostate-specific antigen testing among men aged 55-69 years decreased from a high of 43.1% (95% CI=40.3, 46.1) in 2008 to a low of 32.8% (95% CI=30.8, 34.7) in 2013, with no significant change in 2015 at 33.8% (95% CI=31.3, 36.4). Men aged ≥70 years had consistently high prevalence in all survey years, ranging from 51.1% in 2008 to 36.4% in 2015. African American men, men with a family history of prostate cancer, and other men showed a 5% absolute decrease over time, but this reduction was significant only in other men. Despite decreases, the absolute change in prostate-specific antigen testing for men aged 55-69 years was small (9.3%) over the study period. Men aged ≥70 years, for whom the benefits are unlikely to exceed the harms, continue to have consistently high testing prevalence.

Outcomes of Prostate-specific Antigen-based Prostate Cancer Screening Among Men Using Nonsteroidal Anti-inflammatory Drugs

BackgroundThe Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC), the largest component of the European Randomized Study of Screening for Prostate Cancer (ERSPC), showed a smaller, nonsignificant reduction in prostate cancer–specific mortality by systematic prostate-specific antigen (PSA)-based screening compared with the overall ERSPC results. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation and also PSA elevations due to intraprostatic inflammation. ObjectiveTo explore whether NSAID usage modifies the effects of PSA-based screening on prostate cancer incidence and mortality. Design, setting, and participantsA cohort of 78 165 men from the FinRSPC were linked to a comprehensive national prescription database to obtain information on NSAID reimbursements prior to screening. Outcome measurements and statistical analysisProstate cancer risk and mortality were compared between the FinRSPC screening arm and the control arm among NSAID users and nonusers using an age-adjusted Cox regression model. Results and limitationsScreening increased the detection of Gleason 6 (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.47–1.72 and HR 1.39, 95% CI 1.26–1.54) and localized prostate tumors (HR 1.25, 95% CI 1.18–1.32 and HR 1.11, 95% CI 1.03–1.20) more among baseline NSAID nonusers than among users, respectively (p for interaction <0.04 for both). This difference was observed in all three screening rounds. Detection of metastatic prostate cancer was similar in both NSAID users and nonusers. Screening decreased prostate cancer mortality among men using NSAIDs at FinRSPC randomization (HR 0.66, 95% CI 0.49–0.90) but not among nonusers (HR 0.95, 95% CI 0.81–1.12); p for interaction=0.04. ConclusionsScreening detected fewer well-differentiated localized tumors among NSAID users than among nonusers. This suggests that PSA screening may cause less overdiagnosis within this subgroup, whereas mortality benefit may be greater among NSAID users. Patient summaryProstate cancer screening causes less overdiagnosis of well-differentiated localized prostate tumors among men who use nonsteroidal anti-inflammatory drugs.

Racial differences in prostate-specific antigen–based prostate cancer screening: State-by-state and region-by-region analyses

ObjectiveBlack men are more prone to harbor prostate cancer. They are more likely to succumb to this tumor than their White counterparts and may benefit from early detection and treatment. In this study, we assess the nationwide and regional disparity in prostate-specific antigen (PSA) screening for prostate cancer between Black men and non-Hispanic Whites (NHWs). MethodsA total of 247,079 (weighted 55,185,102) men, aged 40 to 99 years, who responded to the 2012 and 2014 behavioral risk factor surveillance system surveys were used for our analysis. End points consisted of self-reported PSA screening and self-reported nonrecommended PSA screening within 12 months of the interview. The latter was defined as screening in men with <10-year life expectancy. Available sociodemographic variables were used to predict these end points. The independent predictors from multivariate models were used to calculate the adjusted prevalence of PSA screening and nonrecommended PSA screening on a nationwide and regional level. These numbers were calculated for Blacks and NHWs separately and were compared between the 2 groups. ResultsPrevalence of PSA screening was 30.7% in NHWs vs. 28.1% in Blacks (P<0.001). On a region-based analysis, New England, Middle Atlantic, South Atlantic, East North Central, East South Central, West South Central, and Mountain showed a significantly higher rate of PSA screening in NHWs as compared to Blacks (all P<0.001). Middle Atlantic had a significantly higher prevalence of nonrecommended screening in NHWs as compared to Blacks, whereas South Atlantic, West South Central, and Pacific had a significantly higher prevalence of nonrecommended screening in Blacks as compared to NHWs (all P<0.001). Overall, 43 states performed screening more frequently to NHWs, whereas only 8 states performed it more frequently to Black men. The nonrecommended screening was performed more frequently to NHWs in 19 states, whereas 24 states performed it more frequently to Black men. ConclusionOur study demonstrates that on a regional-level (and state-level), there are significant racial differences in overall and nonrecommended PSA screening across the United States. Further research is necessary to identify the reasons for the differences and help overcoming it.

Will magnetic resonance imaging-guided biopsy replace systematic biopsy?

The main disadvantages of the current diagnostic pathway in men with an elevated risk of prostate cancer (PCa) are that: (1) systematic transrectal ultrasound (TRUS) biopsy misses a substantial proportion (20%) of significant PCa because of inherent systematic sampling errors, especially in the anterior gland [1,2]; (2) misclassifies pathologic status including Gleason score (Gl) and tumour stage [3]; and (3) detects a high proportion of men with disease that is unlikely to be harmful (clinically insignificant), with subsequently overtreatments resulting in unintended harm [4]. The latter was the main reason for the U.S. Preventive Services Task Force recommendation against prostate-specific antigenbased screening for prostate cancer in 2012 [5].

Choosing Wisely® in Preventive Medicine: The American College of Preventive Medicine's Top 5 List of Recommendations.

The Choosing Wisely(®) initiative is a national campaign led by the American Board of Internal Medicine Foundation, focused on quality improvement and advancing a dialogue on avoiding wasteful or unnecessary medical tests, procedures, and treatments. The American College of Preventive Medicine (ACPM) Prevention Practice Committee is an active participant in the Choosing Wisely project. The committee created the ACPM Choosing Wisely Task Force to lead the development of ACPM's recommendations with the intention of facilitating wise decisions about the appropriate use of preventive care. After utilizing an iterative process that involved reviewing evidence-based literature, the ACPM Choosing Wisely Task Force developed five recommendations targeted toward overused services within the field of preventive medicine. These include: (1) don't take a multivitamin, vitamin E, or beta carotene to prevent cardiovascular disease or cancer; (2) don't routinely perform prostate-specific antigen-based screening for prostate cancer; (3) don't use whole-body scans for early tumor detection in asymptomatic patients; (4) don't use expensive medications when an equally effective and lower-cost medication is available; and (5) don't perform screening for cervical cancer in low-risk women aged 65 years or older and in women who have had a total hysterectomy for benign disease. The Task Force also reviewed some of the barriers to implementing these recommendations, taking into account the interplay between system and environmental characteristics, and identified specific strategies necessary for timely utilization of these recommendations.

Evidence of prostate cancer “reverse stage migration” toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry

PurposeThe widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. Materials and methodsWe analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. ResultsBetween 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. ConclusionsOver the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality.

Will Magnetic Resonance Imaging-guided Biopsy Replace Systematic Biopsy?

The main disadvantages of the current diagnostic pathway in men with an elevated risk of prostate cancer (PCa) are that: (1) systematic transrectal ultrasound (TRUS) biopsy misses a substantial proportion (20%) of significant PCa because of inherent systematic sampling errors, especially in the anterior gland [1,2]; (2) misclassifies pathologic status including Gleason score (Gl) and tumour stage [3]; and (3) detects a high proportion of men with disease that is unlikely to be harmful (clinically insignificant), with subsequently overtreatments resulting in unintended harm [4]. The latter was the main reason for the U.S. Preventive Services Task Force recommendation against prostate-specific antigenbased screening for prostate cancer in 2012 [5].

Prostate-specific antigen-based prostate cancer screening: Past and future.

Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models.

Prostate-specific Antigen–Based Prostate Cancer Screening: Reduction of Prostate Cancer Mortality After Correction for Nonattendance and Contamination in the Rotterdam Section of the European Randomized Study of Screening for Prostate Cancer

BackgroundLarge randomized screening trials provide an estimation of the effect of screening at a population-based level. The effect of screening for individuals, however, is diluted by nonattendance and contamination in the trial arms. ObjectiveTo determine the prostate cancer (PCa) mortality reduction from screening after adjustment for nonattendance and contamination. Design, setting, and participantsA total of 34 833 men in the core age group, 55–69 yr, were randomized to a screening or control arm in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Prostate-specific antigen (PSA) testing was offered to all men in the screening arm at 4-yr intervals. A prostate biopsy was offered to men with an elevated PSA. The primary end point was PCa-specific mortality. Outcome measurements and statistical analysisNonattendance was defined as nonparticipation in the screening arm. Contamination in the control arm was defined as receiving asymptomatic PSA testing or a prostate biopsy in the absence of symptoms. Relative risks (RRs) were calculated with an intention to screen (ITS) analysis and after correction for nonattendance and contamination using a method that preserves the benefits obtained by randomization. Results and limitationsThe ITS analysis resulted in an RR of 0.68 (95% confidence interval [CI], 0.53–0.89) in favor of screening at a median follow-up of 13 yr. Correction for both nonattendance and contamination resulted in an RR of 0.49 (95% CI, 0.27–0.87) in favor of screening. ConclusionsPCa screening as conducted in the Rotterdam section of the ERSPC can reduce the risk of dying from PCa up to 51% for an individual man choosing to be screened repeatedly compared with a man who was not screened. This benefit of screening should be balanced against the harms of overdiagnosis and subsequent overtreatment. Trial registrationISRCTN49127736.

Can Prostate Specific Antigen Velocity Thresholds Decrease Insignificant Prostate Cancer Detection?

A controversy of current prostate specific antigen based prostate cancer screening is the over detection of potentially insignificant prostate cancer. Because PSA kinetics were previously linked to prostate cancer specific mortality, we determined whether prostate specific antigen velocity is associated with clinically significant prostate cancer. A total of 1,073 men underwent radical prostatectomy from 1992 to 2008 with data available on prostate specific antigen velocity and tumor volume. Insignificant cancer was defined by the Ohori criteria as organ confined, tumor volume 0.5 cc or less and no primary or secondary Gleason pattern 4 or 5. We calculated the proportion of men with pathologically insignificant prostate cancer stratified by prostate specific antigen velocity. Preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year was significantly associated with high grade disease (p = 0.008), positive surgical margins (p = 0.003) and seminal vesicle invasion (p = 0.007) at radical prostatectomy. Median tumor volume was also significantly higher in men with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year (3.1 vs 2.4 cc, p = 0.0001). Overall 69 men (6%) met the Ohori criteria for insignificant cancer. Patients with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year were 50% less likely to have insignificant disease (10% vs 5%, p = 0.003). A prostate specific antigen velocity threshold of 0.4 ng/ml per year was associated with the likelihood of insignificant prostate cancer. This suggests that prostate specific antigen velocity may be a useful adjunct in prostate cancer screening to increase specificity for identifying patients with clinically significant disease.