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Prostate-specific antigen testing for prostate cancer: Depleting a limited pool of susceptible individuals?

ABSTRACT: After the introduction of the prostate specific antigen (PSA) test in the 1980s, a sharp increase in the incidence rate of prostate cancer was seen in the United States. The age-specific incidence patterns exhibited remarkable shifts to younger ages, and declining rates were observed at old ages. Similar trends were seen in Norway. We investigate whether these features could, in combination with PSA testing, be explained by a varying degree of susceptibility to prostate cancer in the populations. We analyzed incidence data from the United States' Surveillance, Epidemiology, and End Results program for 1973-2010, comprising 511,027 prostate cancers in men ?40 years old, and Norwegian national incidence data for 1953-2011, comprising 113,837 prostate cancers in men ?50 years old. We developed a frailty model where only a proportion of the population could develop prostate cancer, and where the increased risk of diagnosis due to the massive use of PSA testing was modelled by encompassing this heterogeneity in risk. The frailty model fits the observed data well, and captures the changing age-specific incidence patterns across birth cohorts. The susceptible proportion of men is [Formula: see text] in the United States and [Formula: see text] in Norway. Cumulative incidence rates at old age are unchanged across birth cohort exposed to PSA testing at younger and younger ages. The peaking cohort-specific age-incidence curves of prostate cancer may be explained by the underlying heterogeneity in prostate cancer risk. The introduction of the PSA test has led to a larger number of diagnosed men. However, no more cases are being diagnosed in total in birth cohorts exposed to the PSA era at younger and younger ages, even though they are diagnosed at younger ages. Together with the earlier peak in the age-incidence curves for younger cohorts, and the strong familial association of the cancer, this constitutes convincing evidence that the PSA test has led to a higher proportion, and an earlier timing, of diagnoses in a limited pool of susceptible individuals.

SUBMITTER: Valberg M

PROVIDER: S-EPMC5468491 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Prostate-specific antigen testing for prostate cancer: Depleting a limited pool of susceptible individuals?

Valberg Morten M Grotmol Tom T Tretli Steinar S Veierød Marit B MB Moger Tron A TA Devesa Susan S SS Aalen Odd O OO

European journal of epidemiology 20160718 6

After the introduction of the prostate specific antigen (PSA) test in the 1980s, a sharp increase in the incidence rate of prostate cancer was seen in the United States. The age-specific incidence patterns exhibited remarkable shifts to younger ages, and declining rates were observed at old ages. Similar trends were seen in Norway. We investigate whether these features could, in combination with PSA testing, be explained by a varying degree of susceptibility to prostate cancer in the populations ...[more]

PMID: 27431530

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Project description:PURPOSE:To examine whether age-related reference ranges for "normal" prostate-specific antigen (PSA) change (determined in men without prostate cancer) can be used to identify men at high risk of having prostate cancer. METHODS:Subjects were men aged 50-69 years with PSA < 10 ng/mL from the UK-based Prostate Testing for cancer and Treatment (ProtecT) study. Men with prostate cancer were categorized as high or low risk of progression (Low risk: Gleason score ≤ 6 and stage T1-T2a; High risk: Gleason score 7-10 or stage T2C). Men without prostate cancer were those with no histological confirmation of prostate cancer. Previously developed longitudinal reference ranges for normal age-related PSA change were used to calculate an age-specific PSA threshold. We compared the ability of our age-specific PSA threshold to discriminate between high- and no/low-risk prostate cancer with that of two existing thresholds: (i) threshold of PSA = 3 ng/ml for all ages; (ii) National Institute of Clinical Excellence (NICE) guidelines dependent on age-group thresholds (age 50-59: PSA = 3 ng/mL; age 60-70: PSA = 4 ng/mL; age ≥ 70: PSA = 5 ng/mL). RESULTS:We included 823 men with high-risk prostate cancer and 80,721 men with no/low-risk prostate cancer. A threshold of PSA = 3 ng/ml for all ages identified more high-risk prostate cancers, recommending biopsy in 9.8% of men, of which 10.3% (n = 823) had high-risk prostate cancer. Using the NICE guidelines as the threshold for biopsy, 6.9% men were recommended for biopsy, of which 11.9% (n = 668) had high-risk prostate cancer. Using the new age-specific threshold for biopsy, 2.3% men were recommended for biopsy, of which 15.2% (n = 290) had high-risk prostate cancer. The age-specific threshold identified fewer high-risk prostate cancers, but fewer men received unnecessary biopsy. CONCLUSION:There is no benefit to using reference ranges for "normal" PSA that change with age nor the age-specific thresholds suggested by the NICE guidelines. While the age-varying thresholds are more discriminatory, too many high-risk cancers are missed.

Project description:ImportanceThe diagnostic activity for prostate cancer has increased during the past decades. However, the benefit and harm of the increased diagnostic activity have not been quantified in detail for a country or a large region.ObjectiveThe aim of this study was to evaluate and quantify the association between increases in diagnostic activity driven by prostate-specific antigen testing and incidence of prostate cancer diagnosis, treatment, and mortality.Design, setting, and participantsThis cohort study used the Proxy-Based Risk-Stratified Incidence Simulation Model-Prostate Cancer to examine observed data on all Swedish men with prevalent prostate cancer and compare them with a corresponding, hypothetical, simulated scenario with more restrictive diagnostic activity. All men aged 40 to 100 years living in Sweden during the time period 1996 to 2016 with incident and prevalent prostate cancer were included. The second scenario is the corresponding, hypothetical, simulated scenario where diagnostic activity remained constant as of 1996 (the beginning of the prostate-specific antigen testing era) throughout the study period.ExposuresHigh or low diagnostic activity for prostate cancer.Main outcomes and measuresIncidence of prostate cancer diagnosis, treatment (deferred treatment, curative treatment, and hormonal treatment), and prostate cancer mortality.ResultsDuring the study period from 1996 to 2016, 188 884 men were diagnosed with prostate cancer at a median (interquartile range) age of 71 (64-77) years. Compared with the low-diagnostic activity scenario, in the high-diagnostic activity scenario, the number of men diagnosed with prostate cancer was 48% higher (423 vs 286 [95% CI, 271-302] per 100 000 men per year), 148% more men were diagnosed with low- or intermediate-risk cancer (221 vs 89 [95% CI, 73-105] per 100 000 men per year), and 108% more men received curative treatment (152 vs 73 [95% CI: 66-85] per 100 000 men per year). There were up to 15% fewer prostate cancer deaths in the scenario with high-diagnostic activity (incidence rate ratio, 0.85; 95% CI, 0.82-0.88).Conclusions and relevanceThis study's results suggest that increased prostate-specific antigen testing and diagnostic activity are associated with a larger number of men being diagnosed with prostate cancer, predominately with low- and intermediate-risk disease. The increased diagnostic activity was associated with a 2-fold increase in curative treatment and a modest decrease in mortality.

Project description:PurposeThe risk of biochemical recurrence is inversely related to the relapse-free interval after radical prostatectomy. We examined predictors of late biochemical recurrence, and the relationship between timing of biochemical recurrence and long-term survival outcomes.Materials and methodsOf 10,609 men treated with radical prostatectomy 1,684 had biochemical recurrence. We examined predictors of late biochemical recurrence (more than 10 years after radical prostatectomy), and calculated metastasis-free and cancer specific survival rates from the time of biochemical recurrence. In the subset of 1,583 men with an undetectable prostate specific antigen at 10 years we calculated actuarial metastasis-free and cancer specific survival estimates at 20 years after radical prostatectomy.ResultsOf the biochemical recurrence studied 77.0%, 16.6%, 4.9% and 1.5% occurred at 5 or less, greater than 5 to 10, greater than 10 to 15 and more than 15 years postoperatively. Late recurrence was associated with more favorable pathological features, as well as higher metastasis-free and cancer specific survival rates. For men with an undetectable prostate specific antigen at 10 years the actuarial probability of biochemical recurrence and metastasis at 20 years varied by stage and grade, with no metastases in patients with a prostatectomy Gleason score 6 or less. A single patient with an undetectable prostate specific antigen at 10 years died of prostate cancer within 20 years after radical prostatectomy.ConclusionsMen with an undetectable prostate specific antigen for more than 10 years have a low risk of subsequent biochemical recurrence, with correspondingly lower rates of metastasis and death. These patients should be counseled that their risk of subsequent cancer related morbidity and mortality is low. Furthermore, these results suggest that annual prostate specific antigen testing may be safely discontinued after 10 years for men with a prostatectomy Gleason score 6 or less and/or limited life expectancy.

Project description:ImportanceDespite guidelines recommending against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, PSA screening remains common.ObjectiveTo identify clinician characteristics associated with PSA screening rates in older veterans stratified by life expectancy.Design, setting, and participantsCross-sectional study of 826 286 veterans 65 years or older eligible for PSA screening who had VA laboratory tests performed in 2011 in the VA health care system.Main outcomes and measuresThe primary outcome was the percentage of men with a screening PSA test in 2011. Limited life expectancy was defined as age of at least 85 years with Charlson comorbidity score of 1 or greater or age of at least 65 years with Charlson comorbidity score of 4 or greater. Primary predictors were clinician characteristics including degree-training level, specialty, age, and sex. We performed log-linear Poisson regression models for the association between each clinician characteristic and PSA screening stratified by patient life expectancy and adjusted for patient demographics and clinician clustering.ResultsIn 2011, 466 017 (56%) of older veterans received PSA screening, including 39% of the 203 717 men with limited life expectancy. After adjusting for patient demographics, higher PSA screening rates in patients with limited life expectancy was associated with having a clinician who was an older man and was no longer in training. The PSA screening rates ranged from 27% for men with a physician trainee to 42% for men with an attending physician (P < .001); 22% for men with a geriatrician to 82% for men with a urologist as their clinician (P < .001); 29% for men with a clinician 35 years or younger to 41% for those with a clinician 56 years or older (P < .001); and 38% for men with a female clinician older than 55 years vs 43% for men with a male clinician older than 55 years (P < .001).Conclusions and relevanceMore than one-third of men with limited life expectancy received PSA screening. Men whose clinician was a physician trainee had substantially lower PSA screening rates than those with an attending physician, nurse practitioner, or physician assistant. Interventions to reduce PSA screening rates in older men with limited life expectancy should be designed and targeted to high-screening clinicians- older male, nontrainee clinicians-for greatest impact.

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Prostate-specific antigen testing for prostate cancer: Depleting a limited pool of susceptible individuals?

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Prostate-specific antigen testing for prostate cancer: Depleting a limited pool of susceptible individuals?

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