Prostate Cancer Screening Strategies Research Articles

Assessment of age specific serum Prostate Specific Antigen (PSA) levels for Indian population: A retrospective analysis at a tertiary healthcare facility.

Prostate-specific antigen (PSA) is a key marker for prostate cancer screening, but its utility is debated, prompting exploration of PSA derivatives for improved accuracy. While racial variations in serum PSA levels are documented, limited data exists for the Indian population. Given increasing life expectancy and heightened awareness of prostate cancer, this study aims to establish age-specific PSA ranges in an Indian cohort, contributing vital insights for population-specific screening and diagnosis. A cross-sectional study was conducted on 4860 men with lower urinary tract symptoms (LUTS). Data, collected from April 2016 to March 2023, included age, PSA levels, digital rectal examination (DRE), and biopsy results. Statistical analysis involved Spearman's correlation, descriptive statistics, and confidence intervals. Of the studied participants, 809 underwent prostatic biopsy, revealing malignancy in 500 cases. Age-specific PSA values were studied in 4170 subjects and showed positive correlation with increasing age and prostate size. Most cancers were metastatic (66%), emphasizing the need for early detection. Age-specific PSA ranges were lower in the Indian population compared to the West. This study's Indian cohort exhibited higher PSA values than some previous Indian studies but lower than Western populations, aligning with global trends. The rising incidence of prostate cancer in India underscores the importance of understanding the disease burden. PSA levels exhibit race-specific variations, cautioning against direct extrapolation of Western data to the Indian population. This study contributes age-specific PSA ranges for an Indian cohort, facilitating nuanced prostate cancer screening strategies.

Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer

BackgroundThe European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age. ObjectiveTo analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2–4 yr). Design, setting, and participantsWe evaluated 25589 men aged 55–59 yr, 16898 men aged 60–64 yr, and 12936 men aged 65–69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2–4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU). Outcome measurements and statistical analysisWe assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60–61 yr. Results and limitationsThe overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2–1.5% for men with PSA <1.0 ng/ml to 13.3–13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60–61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60–61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68–70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76–78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. ConclusionsIn all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55–69 yr is a strong indicator to delay or stop further screening. Patient summaryIn prostate cancer screening, the patient’s baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.

Mutation spectrum and rates of variants of uncertain significance among African American males undergoing prostate cancer germline testing: Need for equity in genetic testing.

10502 Background: Germline testing (GT) for prostate cancer (PCA) is central to metastatic disease management, PCA screening strategies, and hereditary cancer assessment. African American (AA) males have a higher burden of PCA, yet have lower engagement in germline testing which limits understanding of genetic contribution to PCA. Here we evaluated the germline spectrum of AA and White males with PCA undergoing clinical multigene panel testing (MGPT) to inform germline testing strategies with attention to equity. Methods: Study participants included AA men and White men with PCA who underwent a 14-gene MGPT between April 2012 - December 2020 at a clinical diagnostic laboratory (Ambry Genetics). Exclusions were men with known pathogenic variants reported in their families or who had prior genetic testing. MGPT included: ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, TP53. Sanger or next generation sequencing analysis was performed per standard clinical testing protocol. Variant classification was per ACMG 5-tier system. Descriptive statistics summarized results with counts and percentages for categorical variables and mean and standard deviation for continuous variables. Data were compared with Fisher’s exact, Chi-squared, two proportion z-test, or two sample t-test, as appropriate. Significance level was set a priori at 0.05. Results: The dataset included genetic and clinical data from 427 males who had undergone MGPT: White males (n = 190; 45.5%) and AA males (n = 237; 55.5%). Mean age at diagnosis was 59 + 9.3 years. Among men whose Gleason score was indicated (72%), 47% had Gleason &gt; = 8. Majority of men indicated having a 1st/2nd degree relative with PCA (68.97%) or 1st/2nd degree relative with any cancer (99.2%). In the entire cohort, 8.2% tested positive for a pathogenic/likely pathogenic variant; AA males (n = 14, 5.91%) and White males (n = 21, 11.05%). VUS only was reported in 21.31% of the overall cohort with a significant difference noted between AA and White males (25.32% vs. 16.32%, respectively; p = 0.0238). Mutation spectrum in AA males included: BRCA2 (n = 7), PALB2 (n = 3), ATM (n = 3), and BRCA1 (n = 1). Among White males, a wider spectrum of mutations was observed: BRCA2 (n = 6), ATM (n = 5), HOXB13 (n = 5), CHEK2 (n = 2), TP53 (n = 1), and NBN (n = 2). The proportion of AA males with multiple VUS was significantly higher than for Caucasian males (5.1% vs. 0.53%, p = 0.003). Conclusions: Clinical germline testing among AA males reveals a narrow spectrum of mutations in key DNA repair genes, with important implications for precision therapy and hereditary cancer assessment. Furthermore, AA males had significantly higher rates of multiple VUS, indicating critical need for greater inclusion of diverse populations in genetic studies to discern the pathogenic spectrum contributing to PCA aggressiveness and risk.

Evaluation of Prostate Cancer Screening Strategies in a Low-Resource, High-risk Population in the Bahamas

The benefit of prostate-specific antigen screening may be greatest in high-risk populations, including men of African descent in the Caribbean. However, organized screening may not be sustainable in low- and middle-income countries. To evaluate the expected population outcomes and resource use of conservative prostate-specific antigen screening programs in the Bahamas. Prostate cancer incidence from GLOBOCAN and prostate-specific antigen screening data for 4300 men from the Bahamas were used to recalibrate 2 decision analytical models previously used to study prostate-specific antigen screening for Black men in the United States. Data on age and results obtained from prostate-specific antigen screening tests performed in Nassau from 2004 to 2018 and in Freeport from 2013 to 2018 were used. Data were analyzed from January 15, 2021, to March 23, 2022. One or 2 screenings for men aged 45 to 60 years and conservative criteria for biopsy (prostate-specific antigen level >10 ng/mL) and curative treatment (Gleason score ≥8) were modeled. Categories of Gleason scores were 6 or lower, 7, and 8 or higher, with higher scores indicating higher risk of cancer progression and death. Projected numbers of tests and biopsies, prostate cancer (over)diagnoses, lives saved, and life-years gained owing to screening from 2022 to 2040. In this decision analytical modeling study, screening histories from 4300 men (median age, 54 years; range, 13-101 years) tested between 2004 and 2018 at 2 sites in the Bahamas were used to inform the models. Screening once at 60 years of age was projected to involve 40 000 to 42 000 tests (range between models) and prevent 500 to 600 of 10 000 to 14 000 prostate cancer deaths. Screening at 50 and 60 years doubled the number of tests but increased lives saved by only 15% to 16%. Among onetime strategies, screening once at 60 years of age involved the fewest tests per life saved (74-84 tests) and curative treatments per life saved (1.2-2.8 treatments). The findings of this decision analytical modeling study of prostate cancer screening in the Bahamas suggest that limited screening offered modest benefits that varied with screening ages and number of tests. The results can be combined with data on capacity constraints and evaluated relative to competing national public health priorities.

Using a Modified Delphi Approach to Gain Consensus on Relevant Comparators in a Cost-Effectiveness Model: Application to Prostate Cancer Screening.

ObjectiveChallenges can exist when framing the decision question in a cost-effectiveness analysis, particularly when there is disagreement among experts on relevant comparators. Using prostate cancer screening and recent developments in risk stratification, early-detection biomarkers, and diagnostic technologies as a case study, we report a modified Delphi approach to handle decision-question uncertainty.MethodsThe study involved two rounds of anonymous online questionnaires to identify the prostate cancer screening strategies that international researchers, clinicians and decision makers felt important to consider in a cost-effectiveness model. Both purposive and snowball sampling were used to recruit experts. The questionnaire was based on a review of the literature and was piloted for language, comprehension and ease of use prior to dissemination. In Round 1, respondents indicated their preferred screening strategy (including no screening) through a series of multiple-choice questions. The responses informed a set of 13 consensus statements, which respondents ranked their agreement with on a 9-point Likert scale (Round 2). Consensus was considered reached if > 70% of participants indicated agreement and < 15% indicated disagreement.ResultsTwenty participants completed Round 1 and 17 completed Round 2. Consensus was shown towards comparing no formal screening, age-based, and risk-based strategies. The risk-based approaches included screening only higher-risk men, using shorter screening intervals for higher-risk men, screening higher-risk men at an earlier age, and tailoring screening intervals based on prostate-specific antigen (PSA) level at a previous test. There was agreement that inclusion of MRI in the pathway should be considered, but disagreement on the inclusion of new biomarkers.ConclusionIn disease areas where technologies are rapidly evolving, a modified Delphi approach provides a useful tool to identify relevant comparators in an economic evaluation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-021-01009-6.

Impact on prostate cancer clinical presentation after non-screening policies at a tertiary-care medical center- a retrospective study

BackgroundIn May 2012 the US Preventive Task Force issued a ‘D’ recommendation against routine PSA-based early detection of prostate cancer. This recommendation was implemented progressively in our health system. The aim of this study is to define its impact on prostate cancer staging at a tertiary care institution.MethodsA retrospective analysis was performed from 2012 until 2015 at a single center. We analyzed the total number of biopsies performed per year and the positive biopsy rate. For those patients with positive biopsies we recorded diagnostic PSA, clinical stage, ISUP grade group, nodal involvement and metastatic status at diagnosis.ResultsA total of 1686 biopsies were analyzed. The positive biopsy rate increased from 25% in 2012 to 40% in 2015 (p < 0.05). No change in median PSA was noticed (p = 0.627). The biopsies detected higher ISUP grades (p = 0.000). In addition, newly diagnosed prostate cancer presented a higher clinical stage (p = 0.005), higher metastatic rates (p = 0.03) and a tendency to higher lymph node involvement although not statistically significant (p = 0.09).ConclusionAfter the 2012 recommendation, patients presented a higher probability of a prostate cancer diagnosis, with a more adverse ISUP group, clinical stage and metastatic disease.These results should be taken into consideration to implement a risk adapted strategy for prostate cancer screening.

Redesigning Prostate Cancer Screening Strategies to Reduce Overdiagnosis

It is remarkable that even though 30 years have passed since the introduction of prostate-specific antigen (PSA)2 into US clinical practice, researchers and clinicians are still debating its value for prostate cancer screening. The US Preventive Services Task Force has seesawed from stating that PSA testing was a personal decision for the individual man in 2008, to concluding “moderate or high certainty that … the harms outweigh the benefits” in 2012, to recommending shared decision-making once again in 2018 (1). In most industrialized countries, government-sanctioned guideline groups recommend against population-based screening, yet PSA testing remains common in everyday practice throughout the Western world. My own view is that the PSA debate has lost the forest for the trees. White papers and recommendation statements focus on subtle points of scientific methodology—such as whether postrandomization consent results in the loss of allocation concealment—while giving sparse attention to some larger facts and principles. Here, I lay out 3 simple, established, and accepted propositions about PSA screening and argue that these lead to some straightforward conclusions. For many years, it was open to reasonable debate as to whether PSA screening did, in fact, reduce prostate cancer mortality. Recent data have ended this debate. There has been only 1 methodologically acceptable randomized trial of PSA screening, the European Randomised Study of Screening for Prostate Cancer (ERSPC), and this trial clearly showed a reduction in prostate cancer mortality (2). Similarly, recent US population trends showing reductions of 40% to 50% in prostate cancer mortality since the pre-PSA era cannot be explained without reference to a screening effect (3). The harms of PSA screening, on the other hand, are well known. Prostate cancer generally has a very indolent course, such that a large proportion of screen-detected cancers would never have been diagnosed during the patient's …

Cost-effectiveness of prostate cancer screening: a systematic review of decision-analytical models

BackgroundThere is ongoing debate about the harms and benefits of a national prostate cancer screening programme. Several model-based cost-effectiveness analyses have been developed to determine whether the benefits of prostate cancer screening outweigh the costs and harms caused by over-detection and over-treatment, and the different approaches may impact results.MethodsTo identify models of prostate cancer used to assess the cost-effectiveness of prostate cancer screening strategies, a systematic review of articles published since 2006 was conducted using the NHS Economic Evaluation Database, Medline, EMBASE and HTA databases. The NICE website, UK National Screening website, reference lists from relevant studies were also searched and experts contacted. Key model features, inputs, and cost-effectiveness recommendations were extracted.ResultsTen studies were included. Four of the studies identified some screening strategies to be potentially cost-effective at a PSA threshold of 3.0 ng/ml, including single screen at 55 years, annual or two yearly screens starting at 55 years old, and delayed radical treatment. Prostate cancer screening was modelled using both individual and cohort level models. Model pathways to reflect cancer progression varied widely, Gleason grade was not always considered and clinical verification was rarely outlined. Where quality of life was considered, the methods used did not follow recommended practice and key issues of overdiagnosis and overtreatment were not addressed by all studies.ConclusionThe cost-effectiveness of prostate cancer screening is unclear. There was no consensus on the optimal model type or approach to model prostate cancer progression. Due to limited data availability, individual patient-level modelling is unlikely to increase the accuracy of cost-effectiveness results compared with cohort-level modelling, but is more suitable when assessing adaptive screening strategies. Modelling prostate cancer is challenging and the justification for the data used and the approach to modelling natural disease progression was lacking. Country-specific data are required and recommended methods used to incorporate quality of life. Influence of data inputs on cost-effectiveness results need to be comprehensively assessed and the model structure and assumptions verified by clinical experts.

Can PSA Reflex Algorithm be a valid alternative to other PSA-based prostate cancer screening strategies?

The available laboratory tests for the differential diagnosis of prostate cancer, are represented by the total PSA, the free PSA, and the free/total PSA ratio. In Italy most of doctors tend to request both total and free PSA for their patients even in cases where the total PSA doesn't justify the further request of free PSA, with a consequent growth of the costs for the National Health System. The aim of our study was to predict the saving in Euro (due to reagents) and reduction in free PSA tests, applying the "PSA Reflex" algorithm. We calculated the number of total PSA and free PSA exams performed in 2014 in the Hospital of Grosseto and, simulating the application of the "PSA Reflex" algorithm in the same year, we calculated the decrease in the number of free PSA requests and we tried to predict the Euro savings in reagents, obtained from this reduction. In 2014 in the Hospital of Grosseto 25,955 total PSA tests have been performed: 3,631 (14%) resulted greater than 10 ng / ml; 7,686 (29.6%) between 2 and 10 ng / ml; 14,638 (56.4%) lower than 2 ng / ml. The performed free PSA tests were 16904. Simulating the use of "PSA Reflex" algorithm, the free PSA tests would be performed only in cases with total PSA values between 2 and 10 ng / mL with a saving of 54.5% of free PSA exams and of 8,971 euros, only for reagents. Our study showed that the "PSA Reflex" algorithm is a valid alternative leading to a reduction of the costs. The estimated intralaboratory savings, due to the reagents, seem to be modest, however, they are followed by the additional savings due to the other diagnostic processes for prostate cancers.

Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11year historical population follow-up study of more than 1 million men.

Aims/hypothesisAn inverse association has consistently been shown between diabetes and prostate cancer incidence. We investigated whether lower prostate cancer incidence among men with diabetes is attributable to lower detection due to prostate cancer screening patterns.MethodsWe studied a population-based historical cohort of 1,034,074 Israeli men aged 21–90 years, without a previous history of cancer. The cohort was followed-up from 2002 to 2012, according to diabetes morbidity, for frequency of prostate-specific antigen (PSA) testing, mean PSA values and detection of prostate cancer, after adjustment for age, ethnic origin, socioeconomic status and PSA testing.ResultsIn January 2002, 74,756 men had prevalent diabetes. During the 11 year follow-up, 765,483 (74%) remained diabetes-free and 193,835 developed diabetes. Approximately 10% more PSA screening was performed in men with than without diabetes, but the rate of PSA positivity (>4 μg/l) was 20% lower in men with diabetes. PSA values were already significantly lower in men who developed diabetes than in those who did not, 3 years before diabetes diagnosis. Reduced prostate cancer risk was observed among men with incident diabetes only for low–moderate grade tumours (Gleason score 2–6: adjusted HR 0.83; 95% CI 0.77, 0.89). No association was observed for high-grade tumours (Gleason score 7–10: HR 0.99; 95% CI 0.88, 1.11).Conclusions/interpretationOur findings suggest that diabetes comorbidity is a factor to be considered in prostate cancer screening strategies, and specifically in the interpretation of PSA levels. Furthermore, our demonstration of reduced incidence of low–moderate grade but not high-grade prostate cancer tumours among men with diabetes supports the possibility that low PSA levels, rather than lower tumour risk, explains the observed reduced incidence of prostate cancer in men with diabetes.Trial registration:ClinicalTrials.gov NCT02072902

MP86-14 DOES A SECOND CONFIRMATORY PSA ABOVE 4.0NG/ML LEAD TO THE DIAGNOSIS OF MORE CLINICALLY SIGNIFICANT PROSTATE CANCER?

INTRODUCTION AND OBJECTIVES: The optimal strategy for prostate cancer screening has yet to be defined. Traditional strategies of prostate cancer screening have lead to high rates of over-diagnosis and over-treatment. Several clinical guidelines recommend that a single PSA value warrants a prostate biopsy. In 2009, the Portland VA changed their policy regarding the recommendation of a prostate biopsy to requiring a second (confirmatory) PSA value >4.0ng/ml. The goal of this study was to evaluate whether a confirmatory PSA value >4.0ng/ml increased the detection of clinically significant prostate cancer. METHODS: Subjects were identified utilizing The VA Corporate Data Warehouse electronic database. Data were retrospectively collected from 9/1/2009 and 9/1/2013. The data were divided into 3 groups to evaluate the effect of policy changes on cancer detection. Period 1 was from 9/1/2009 to 9/2/2011, prior to the use of a confirmatory PSA. Period 2 was from 9/2/2011-5/1/2012, prior to the USPTF recommendation. Period 3 was from 5/2012-9/1/2013. Age, Race, PSA, PSA Density (PSAD), Gleason Score, T stage, and NCCN risk categories were compared between these time period groups using Spearman’s Rank Correlation and Mann-Whitney U test. RESULTS: A total of 1054 patients were enrolled between 9/1/ 2009 and 9/1/2013. Study population of Period 1; n 1⁄4 600, Period 2; n 1⁄4 205, and Period 3; n 1⁄4 249. Mean age was 64.7 (SD 6.0), Median PSA was 5.8 ng/ml (IQR 1⁄4 3.9). Mean prostate volume was 51.6 cc. Age, Race, PSA, and prostate volume were compared between these groups and were not statistically significant (p 1⁄4.253, p 1⁄4.543, p 1⁄4.674, p 1⁄4.863; respectively). Cancer cases were categorized by NCCN Risk: Low (n1⁄4131), Intermediate (n1⁄4222), and High (n1⁄4160). A Mann-Whitney U Test was performed to determine if observed NCCN risk was higher in patients biopsied after our policy change (period 2) or after the USPSTF recommendation (period 3). No change was observed in the three groups (p 1⁄4.200). A Spearman’s Rank Correlation was calculated to examine if there was a correlation between the groups (Period 1, Period 2, and Period 3) and a High NCCN risk. The relationship was marginally significant (p 1⁄4.061), with a weak negative correlation (-.083). This test was repeated to determine if a correlation existed between the three groups and Intermediate-High NCCM risk. This relationship was significant (p 1⁄4.035) with a weak negative correlation (-.093). CONCLUSIONS: The policy change requiring a confirmatory PSA value>4.0 ng/ml has not led to an increase in NCCN intermediateor high-risk prostate cancer.

Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African-American men.

Men with a family history of prostate cancer and African-American men are at high risk for prostate cancer and in need of personalized risk estimates to inform screening decisions. This study evaluated genetic variants in genes encoding microRNA (miRNA) binding sites for informing of time to prostate cancer diagnosis among ethnically diverse, high-risk men undergoing prostate cancer screening. The Prostate Cancer Risk Assessment Program (PRAP) is a longitudinal screening program for high-risk men. The eligibility includes men aged between 35 and 69 years with a family history of prostate cancer or African descent. Participants with 1 follow-up visit were included in the analyses (n=477). Genetic variants in genes encoding miRNA binding sites (ALOX15 (arachidonate 15-lipooxygenase), IL-16, IL-18 and RAF1 (v-raf-1 murine leukemia viral oncogene homolog 1)) previously implicated in prostate cancer development were evaluated. Genotyping methods included Taqman SNP Genotyping Assay or pyrosequencing. Cox models were used to assess time to prostate cancer diagnosis by risk genotype. Among 256 African Americans with one follow-up visit, the TT genotype at rs1131445 in IL-16 was significantly associated with earlier time to prostate cancer diagnosis vs the CC/CT genotypes (P=0.013), with a suggestive association after correction for false discovery (P=0.065). Hazard ratio after controlling for age and PSA for TT vs CC/CT among African Americans was 3.0 (95% confidence interval: 1.26-7.12). No association with time to diagnosis was detected among Caucasians by IL-16 genotype. No association with time to prostate cancer diagnosis was found for the other miRNA target genotypes. Genetic variation in IL-16 encoding miRNA target site may be informative of time to prostate cancer diagnosis among African-American men enrolled in prostate cancer risk assessment, which may inform individualized prostate cancer screening strategies in the future.

Validation of association of genetic variants at 10q with prostate‐specific antigen (PSA) levels in men at high risk for prostate cancer

To validate six previously identified markers among men at increased risk of prostate cancer (African-American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study. Eligibility criteria for PRAP include age 35-69 years with a family history of prostate cancer, African-American ethnicity regardless of family history, and known BRCA gene mutations. The genome-wide association study markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12) and rs17632542 (19q13.33). Genotyping methods included either the Taqman(®) single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders. A total of 707 participants (37% Caucasian, 63% African-American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) was strongly associated with PSA levels among Caucasian participants in the high-risk group (P < 0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) was found to be associated with PSA level (P = 0.03) in Caucasian men in the high-risk group, with a 15% increase in PSA level with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 was proposed, specific to high-risk Caucasian men. Genetic variation at 10q may be particularly important in personalizing the interpretation of PSA level for Caucasian men in the high-risk group. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for Caucasian men in the high-risk group, although further study is warranted.

Comparative effectiveness of alternative prostate-specific antigen--based prostate cancer screening strategies: model estimates of potential benefits and harms.

The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits. To evaluate comparative effectiveness of alternative PSA screening strategies. Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies. National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality. A contemporary cohort of U.S. men. Lifetime. Societal. 35 screening strategies that vary by start and stop ages, screening intervals, and thresholds for biopsy referral. PSA tests, false-positive test results, cancer detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved. Without screening, the risk for prostate cancer death is 2.86%. A reference strategy that screens men aged 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%. A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%. Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions. The model is a simplification of the natural history of prostate cancer, and improvement in survival due to screening is uncertain. Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives. National Cancer Institute and Centers for Disease Control and Prevention.

Toward a rational strategy for prostate cancer screening based on long-term risk of prostate cancer metastases and death: Data from a large, unscreened, population-based cohort followed for up to 30 years.

4512 Background: Prostate-specific antigen (PSA) testing remains controversial due to high number of men need to be screened to prevent one death. Current screening recommendations are based on few data. We analyzed PSA in archived blood plasma collected in 1974–92 as part of the Malmö Preventive Project. This is a large, representative cohort of Swedish men not subject to screening, chiefly accruing at age 44-50 (i.e. shortly before PSA is recommended to begin in US) and followed for up to 30 years. The study is a unique “natural experiment” to understand the association between early PSA and long-term risk of prostate cancer morbidity and mortality. Methods: We conducted a case control study nested within a cohort of 12090 men providing blood in 1974-86 and 4999 providing a repeat sample 6 years later and an independent cohort of 1,167 men with blood provided at age 60. 252 men with carefully ascertained evidence of prostate cancer metastasis or death were matched 3:1 with controls. Anti-coagulated plasma was analyzed using methods shown to give highly accurate PSA values. Results: PSA was strongly associated with risk of prostate cancer death or metastasis up to 30 years later (AUC 0.70, 0.76 and 0.90 at age 44-50, 51-55 and 60 respectively, p<0.005). At age 44-50, 44% of cancer deaths occurred in men with PSA >1.6 ng/ml (top 10%) at a median follow up of 27 years. PSA at median at age 44-50 did not rule out risk of metastases or death but did so in older men: 28%, 18% and 0.5% of metastases occurred in men with PSA at median (<0.7, <0.8 and <1.1 ng/ml at age 44-50, 51-55 and, 60 respectively). The risk of prostate cancer metastasis by 15 years for men with PSA at median was never greater than 0.3% at any age. Conclusions: PSA is highly predictive of long-term risk of prostate cancer morbidity and mortality. Close to half of all deaths could be prevented by intense surveillance of a small proportion of men with the highest PSA levels at age 44-50. For men with lower PSA, testing at age 51-55 and age 60 is sufficient to capture risk of prostate cancer metastases or death 10+ years in advance. This strategy would allow 50% of men to have only three lifetime PSA tests.

Do Margins Matter? The Prognostic Significance of Positive Surgical Margins in Radical Prostatectomy Specimens

Purpose The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy. Materials and Methods We analyzed 1,389 consecutive patients with clinical stage T1–3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate. Results Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% ± 12% and 81% ± 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06–2.16). Conclusions We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.

Prostate cancer screening strategies with re-screening interval determined by individual baseline prostate-specific antigen values are cost-effective

Aims To determine whether prostate cancer screening strategies with re-screening interval determined by individual baseline prostate-specific antigen values are cost-effective. Methods Based on the results of an actual contemporary screening program, we established Markov decision analytic models of prostate cancer screening with personalized re-screening interval strategies using cutoff baseline PSA levels for biennial screening as well as a model of uniformly annual or biennial screening. These strategies were compared in terms of cumulative incidence of early cancer and cost-effectiveness. Results Early cancer detection rates were similar among all strategies. Personalized strategies were more cost-effective compared to uniform screening strategies. If all participants with negative PSA results uniformly omit annual screening, it would be more costly but less effective (dominated). Contrary, annual screening for all participants would cost too much. These results were robust throughout sensitivity analysis incorporating every assumption in the models. Conclusions This study adds important evidence that personalized rescreening strategies based on individual baseline PSA have advantages of cost-effectiveness against conventional uniform strategies.

197: Prostate Cancer Screening Strategies with Rescreening Interval Determined by Individual Baseline Prostate-Specific Antigen Values are Cost-Effective

You have accessJournal of UrologyPodium 4, Sunday, May 20, 2007, 8:00 - 10:00 am1 Apr 2007197: Prostate Cancer Screening Strategies with Rescreening Interval Determined by Individual Baseline Prostate-Specific Antigen Values are Cost-Effective Takashi Kobayashi, Rei Goto, Kazuto Ito, and Osamu Ogawa Takashi KobayashiTakashi Kobayashi More articles by this author , Rei GotoRei Goto More articles by this author , Kazuto ItoKazuto Ito More articles by this author , and Osamu OgawaOsamu Ogawa More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)30462-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "197: Prostate Cancer Screening Strategies with Rescreening Interval Determined by Individual Baseline Prostate-Specific Antigen Values are Cost-Effective." The Journal of Urology, 177(4S), p. 66 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 66 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Takashi Kobayashi More articles by this author Rei Goto More articles by this author Kazuto Ito More articles by this author Osamu Ogawa More articles by this author Expand All Advertisement PDF downloadLoading ...

DO MARGINS MATTER? THE PROGNOSTIC SIGNIFICANCE OF POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY SPECIMENS

The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy. We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate. Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16). We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.

Evaluation of a low-invasive strategy for prostate cancer screening with prostate-specific antigen

Objectives. To evaluate a two-step strategy for the detection of prostate cancer within the context of serial screening and compare this strategy with other screening strategies. The optimal combination of tests proposed for prostate cancer screening remains undetermined, particularly when screening is repeated over time. Methods. A prospective serial prostate cancer screening study with follow-up to 55 months was performed in a general community screening clinic. One thousand seven hundred seven self-referred men, 50 to 75 years old, without a history of prostate cancer agreed to undergo screening for prostate cancer on an annual basis. Serum prostate-specific antigen (PSA) measurement was the first-step screening test. If the serum PSA test was positive, a standard urologic evaluation was performed. Biopsy was recommended only if a test other than serum PSA was suspicious for cancer. The outcome measures were the biopsy rate and prostate cancer detection rate. The comparisons with other studies were age-standardized to correct for differences in age distribution. Results. The biopsy and cancer detection rates after the first test were 7.0% and 2.0%, respectively. After 4 years of the study, the cumulative biopsy rate and cumulative cancer detection rate per enrolled man was 12% and 4.1%, respectively. The comparisons between studies revealed that screening strategies using serum PSA as a first-line test had similar detection rates but lower biopsy rates than strategies performing biopsy when one of several screening tests was positive. Conclusions. A two-step screening strategy using serum PSA alone as the initial test seemed able to detect as many cancers as when all screening tests were used at the same time but reduced the number of unnecessary biopsies.