Population-based Prostate-specific Antigen Research Articles

Modeling Disease Trajectories for Castration-resistant Prostate Cancer Using Nationwide Population-based Data

BackgroundLittle is known about disease trajectories for men with castration-resistant prostate cancer (CRPC). ObjectiveTo create a state transition model that estimates time spent in the CRPC state and its outcomes. Design, setting, and participantsThe model was generated using population-based prostate-specific antigen data from 40% of the Swedish male population, which were linked to nationwide population-based databases. We compared the observed and predicted cumulative incidence of transitions to and from the CRPC state. Outcome measurements and statistical analysisWe measured time spent in the CRPC state and the proportion of men who died of prostate cancer during follow-up by CRPC risk category. Results and limitationsTime spent in the CRPC state varied from 1.1 yr for the highest risk category to 3.9 yr for the lowest risk category. The proportion of men who died from prostate cancer within 10 yr ranged from 93% for the highest risk category to 54% for the lowest. There was good agreement between the model estimates and observed data. ConclusionsThere is large variation in the time spent in the CRPC state, varying from 1 yr to 4 yr according to risk category. Patient summaryIt is possible to accurately estimate the disease trajectory and duration for men with castration-resistant prostate cancer.

Cost-benefit analysis of a population-based prostate-specific antigen mass testing for early detection of prostate cancer in Anambra State, Nigeria: A health provider's perspective

Aims: We conducted a cost-benefit analysis of a population-based prostate-specific antigen (PSA) mass testing for prostate cancer (PCa) from a provider’s perspective to give further insights into the programme’s sustainability at scale-up. Materials and Methods: A cross-sectional study design was adopted. The cost and benefit of the population-based-specific antigen mass testing were estimated using activity-based costing and participants’ willingness to pay (WTP), respectively. The study was conducted in a primary health-care facility in Anambra State, Nigeria. A total of 412 asymptomatic males between 40 and 74 years who had not had a PSA screening within the past five years were recruited for the study. A one-month population-based PSA mass screening for PCa was performed at the primary health-care facility. The cost of population-based PSA mass testing was presented as cost/male screened while benefit was measured as the participants’ minimum WTP analysis amount. Benefit-cost ratio (BCR) served as the primary outcome, with values higher than one signifying a self-sustainable programme. Results: The cost/male screened was USD 13.43 ± 2.26, while the participants’ WTP amount of US$3.99 ± 4.49 to calculate the BCR gave a BCR ratio of 0.3. Conclusion: The estimated BCR showed that the programme would not be sustainable if funding were based solely on participants’ out-of-pocket expenses. Other financing mechanisms, such as donor funds, will be necessary to sustain such public health programmes in Nigeria.

Reimagining prostate cancer screening: the IMPACT of germline mutations.

Structured prostate-specific antigen (PSA) screening allows for the early detection of prostate cancer in men aged 55–69 years with a reduction in the incidence of metastatic disease at presentation and cancer-specific mortality at 16 year's follow-up. 1 Hugosson J Roobol MJ Månsson M et al. A 16-yr follow-up of the European randomized study of screening for prostate cancer. Eur Urol. 2019; 76: 43-51 Summary Full Text Full Text PDF PubMed Scopus (182) Google Scholar Population-based screening has been associated with a non-negligible risk of overdiagnosis (ie, the detection of cancers that would not have caused symptoms), which can be as high as 40%, and has limited its adoption at a large scale 2 Martin RM Donovan JL Turner EL et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA. 2018; 319: 883-895 Crossref PubMed Scopus (210) Google Scholar such that no national prostate cancer screening programmes exist in the USA and Europe. 3 Van Poppel H Hogenhout R Albers P van den Bergh RCN Barentsz JO Roobol MJ A European model for an organised risk-stratified early detection programme for prostate cancer. Eur Urol Oncol. 2021; (published online Aug 4)https://doi.org/10.1016/j.euo.2021.06.006 Summary Full Text Full Text PDF Scopus (11) Google Scholar Restricting the use of repeated PSA testing to men at risk of early-onset disease because of a family history of prostate cancer or germline mutations has been proposed as a means of improving the effectiveness of screening. 2 Martin RM Donovan JL Turner EL et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA. 2018; 319: 883-895 Crossref PubMed Scopus (210) Google Scholar , 4 Gandaglia G Albers P Abrahamsson PA et al. Structured population-based prostate-specific antigen screening for prostate cancer: the European Association of Urology Position in 2019. Eur Urol. 2019; 76: 142-150 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar , 5 Page EC Bancroft EK Brook MN et al. Interim results from the IMPACT study: evidence for prostate-specific antigen screening in BRCA2 mutation carriers. Eur Urol. 2019; 76: 831-842 Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective studyAfter the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. Full-Text PDF Open Access

Impact of prostate-specific antigen screening on tumor size in patients with prostate cancer in a super-aging district in Kyoto, Japan.

Population-based prostate-specific antigen (PSA) screening is effective for reducing prostate cancer (PCa)-related mortality rates. In this study, we assessed biopsy-proven maximum cancer core length (MCCL) and maximum cancer diameter on magnetic resonance imaging (MRI; MCDM) in prostate biopsy and multiparametric MRI (mp-MRI) by PCa detection. We retrospectively assessed 214 male PCa patients and 187 PCa patients with Prostate Imaging Reporting and Data System version 2 (PI-RADS) category 3-5 lesions in pre-biopsy mp-MRI and targeted biopsy characteristics. The mean biopsy-proven MCCL and MCDM were compared among three PSA screening groups, namely the population-based PSA screening (PBS), opportunistic PSA screening (OPS), and symptomatic outpatient PSA examination (SOP) groups. The median age and PSA value of the 214 participants were 75years and 7.9ng/mL, respectively. In the PBS, OPS, and SOP groups, the median ages were 73, 76, and 76years, respectively (p = 0.046); PSA values were 7.2, 9.5, and 11.5ng/mL, respectively (p < 0.001); and biopsy-proven MCCL and MCDM were significantly increased to 7, 10, and 14mm (p < 0.001) and to 11, 15, and 17mm (p < 0.001), respectively. In the 187 PCa patients with PI-RADS category 3-5 lesions on mp-MRI, MCDM were 11, 14, and 17mm (p < 0.001), respectively. The biopsy-proven MCCL and MCDM were significantly smaller in the PBS and OPS groups than in the SOP group, which suggests that PSA screening detected PCa earlier than in symptomatic patients. PSA screening with MRI could objectively lead to earlier diagnosis based on tumor size.

Assessment of prostate-specific antigen screening: an evidence-based report by the German Institute for Quality and Efficiency in Health Care.

Prostate-specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long-term disease-specific mortality, but also results in overdiagnoses and treatment-related harms. To systematically assess the benefits and harms of population-based PSA screening and the potential net benefit to inform health policy decision-makers in Germany. We performed a protocol-guided comprehensive literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. All steps were performed by one or two investigators; any discrepancies were resolved by consensus. To allow subgroup analyses for identifying the optimal screening parameters, the eight national trials conducted under the umbrella of the European Randomised study of Screening for Prostate Cancer (ERSPC) were included as individual trials. We included a total 11 randomised controlled trials (RCTs) with a total of 416 000 study participants. For all-cause mortality, we found neither benefit nor harm. PSA screening was associated with a reduced risk of both prostate cancer mortality and the development of metastases. For the outcomes of health-related quality of life, adverse effects and the consequences of false-negative screening results there was no difference; however, this was due to the lack of eligible RCT data. Finally, PSA screening was associated with large numbers of overdiagnoses with adverse downstream consequences of unnecessary treatment (e.g. incontinence, erectile dysfunction) and large numbers of false-positive PSA tests leading to biopsies associated with a small but not negligible risk of complications. Limitations of this assessment include the clinical heterogeneity and methodological limitations of the underlying studies. The benefits of PSA-based prostate cancer screening do not outweigh its harms. We failed to identify eligible screening studies of newer biomarkers, PSA derivatives or modern imaging modalities, which may alter the balance of benefit to harm. In the present study, we reviewed the evidence on the PSA blood test to screen men without symptoms for prostate cancer. We found that the small benefits experienced by some men do not outweigh the harms to many more men.

Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer: The European Association of Urology Position in 2019

Prostate cancer (PCa) is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55–69yr) using prostate-specific antigen (PSA) is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU) supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. Patient summaryImplementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated.

Prostate Cancer Germline Variations and Implications for Screening and Treatment.

Prostate cancer (PCa) is a highly heritable disease, and rapid evolution of sequencing technologies has enabled marked progression of our understanding of its genetic inheritance. A complex polygenic model that involves common low-penetrance susceptibility alleles causing individually small but cumulatively significant risk and rarer genetic variants causing greater risk represent the current most accepted model. Through genome-wide association studies, more than 100 single-nucleotide polymorphisms (SNPs) associated with PCa risk have been identified. Consistent reports have identified germline mutations in the genes BRCA1, BRCA2, MMR, HOXB13, CHEK2, and NBS1 as conferring moderate risks, with some leading to a more aggressive disease behavior. Considering this knowledge, several research strategies have been developed to determine whether targeted prostate screening using genetic information can overcome the limitations of population-based prostate-specific antigen (PSA) screening. Germline DNA-repair mutations are more frequent in men with metastatic disease than previously thought, and these patients have a more favorable response to therapy with poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors. Genomic information is a practical tool that has the potential to enable the concept of precision medicine to become a reality in all steps of PCa patient care.

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.

The Effects of Population-based Prostate-specific Antigen Screening Beginning at Age 40

To evaluate population-based prostate cancer (CaP) testing of men in their 40s, given the paucity of prospective data evaluating the consequences of prostate-specific antigen (PSA) testing in younger men for CaP. A total of 1052 men in their 40s were followed longitudinally for prostate outcomes, from 1990 to 2010. A random subset of 268 men was selected to undergo biennial CaP testing including PSA testing, transrectal ultrasound, and a digital rectal examination. A representative population of 609 men with a subset of 159 men who also began CaP testing in their 50s was also evaluated as a comparison group. Risk of prostate biopsy (PBx), CaP, or death from CaP was compared between CaP-tested and the routine-care population cohort. Median follow-up was 17.2 years. Men aged 40-49, who underwent CaP testing were 2.4 times more likely to undergo a PBx (hazard ratio [HR] 2.4 95% confidence interval [CI] 1.8-3.3) and 2.2 times more likely to be diagnosed with low-risk CaP (HR 2.2, 95% CI 1.12-4.0). Those initiating CaP testing a decade earlier were 2.2 times and 1.7 times more likely to be biopsied and be diagnosed with CaP for any given age (HR 2.2 95% CI 1.4-3.5 and 1.7 95% CI 1.1-2.7, respectively). CaP testing in men beginning at age 40 resulted in a significant increase in the risk of PBx and diagnosis of low-risk CaP, without a measurable reduction in risk of CaP-death in this low-risk population. However, given the natural history of CaP, a longer follow-up is needed to confirm this finding.

Determinants of participation in prostate cancer screening: a simple analytical framework to account for healthy-user bias.

In Japan at present, fecal occult blood testing (FOBT) is recommended for cancer screening while routine population-based prostate-specific antigen (PSA) screening is not. In future it may be necessary to increase participation in the former and decrease it in the latter. Our objectives were to explore determinants of PSA-screening participation while simultaneously taking into account factors associated with FOBT. Data were gathered from a cross-sectional study conducted with random sampling of 6191 adults in Osaka city in 2011. Of 3244 subjects (return rate 52.4%), 936 men aged 40–64 years were analyzed using log-binomial regression to explore factors related to PSA-screening participation within 1 year. Only responders for cancer screening, defined as men who participated in either FOBT or PSA-testing, were used as main study subjects. Men who were older (prevalence ratio [PR] [95% confidence interval (CI)] = 2.17 [1.43, 3.28] for 60–64 years compared with 40–49 years), had technical or junior college education (PR [95% CI] = 1.76 [1.19, 2.59] compared with men with high school or less) and followed doctors' recommendations (PR [95% CI] = 1.50 [1.00, 2.26]) were significantly more likely to have PSA-screening after multiple variable adjustment among cancer-screening responders. Attenuation in PR of hypothesized common factors was observed among cancer-screening responders compared with the usual approach (among total subjects). Using the analytical framework to account for healthy-user bias, we found three factors related to participation in PSA-screening with attenuated association of common factors. This approach may provide a more sophisticated interpretation of participation in various screenings with different levels of recommendation.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

Background:Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing.Methods:Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50–69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up.Results:Among randomised practices, 271 (68%) in the intervention arm (198 114 men) and 302 (78%) in the control arm (221 929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices).Conclusions:The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Clinical significance of cancer in radical prostatectomy specimens: analysis from a contemporary series of 2900 men

With prostate specific antigen (PSA) testing, up to 49% of detected tumours are small and in some of these cases there is a possibility that the tumour will remain clinically insignificant during the patient's remaining lifetime. The current study was performed to characterise the extent of cancer in men treated by radical prostatectomy (RP) in a community without population-based PSA screening. Clinical and pathological data of 2900 patients who underwent RP between 2008 and 2012 were analysed. Specimens were entirely embedded and evaluated by routine haematoxylin and eosin staining. Tumours were graded using recent modifications to the International Society of Urological Pathology (ISUP) modified Gleason grading system, and staged according to the ISUP recommendations. Tumours were considered pathologically insignificant if organ confined, with a volume of <0.5 cc and a Gleason score (GS) of <7. The mean age of patients in the series was 63 years (range 32-79 years) and the mean pre-operative PSA was 7.16 ng/mL (range 0.4-69). In total, 2614 (90.1%) were classified as cT1; however, insignificant tumours were found in only 150 (5.2%) patients following examination of the radical prostatectomy specimen. A total of 2681 cases (92.4%) had a final GS of ≥7, 1144 (39.4%) had extraprostatic extension (EPE), of which 88.7% were classified as established; 669 (23.1%) had a tumour volume of >3 cc and 284 (9.8%) had surgical margin positivity. Seminal vesicle involvement was seen in 159 (5.5%) cases. Of 693 patients who had a lymphadenectomy, 31 (4.5%) had lymph node metastases. Aged ≤50 years were 212 (7.3%) patients (mean age 47 years). Of these, 194 were classified as cT1 while 192 (90.6%) were found to have significant cancer on examination of the radical prostatectomy specimen. We have shown in our series that although 90.1% of tumours were cT1, an overwhelming majority of tumours were found to be pathologically significant following RP, with a high proportion of cases showing high stage disease, seminal vesicle involvement and lymph node metastasis. These results suggest that, contrary to estimates from international trials, ad hoc PSA testing is associated with low levels of over-treating.

Uptake of prostate‐specific antigen testing for early prostate cancer detection in Sweden

The aim of our study was to estimate uptake of prostate-specific antigen (PSA) testing in an entire country, including time trends and geographical differences. Data from the Swedish Cancer Register on prostate cancer incidence between 1980 and 2007 and published data from the Gothenburg branch of the European randomized study of screening for prostate cancer (ERSPC), a population-based PSA screening study, were used in two models of changes in incidence of prostate cancer as a proxy for uptake of PSA testing in all 24 Swedish counties. The estimated annual PSA testing, irrespective of previous years' exposure, reached a peak of 12% of all men in 2004 and decreased thereafter to 6% in 2007 and varied from less than 5 to 20% between counties. Under the assumption that men who underwent annual PSA testing were previously unexposed to PSA testing, the cumulated uptake of PSA testing in men aged 55-69 years in Sweden increased from zero in 1997 to 56% in 2007. Our study shows that it is possible to estimate uptake of PSA testing in the population from the prostate cancer incidence pattern. There were large geographical variations in uptake of PSA testing despite a uniform health care system in Sweden and there was a substantial increase in the uptake of PSA testing during the study period, despite that there were no national recommendations for PSA-based prostate cancer screening.

Association of obesity with prostate cancer: a case-control study within the population-based PSA testing phase of the ProtecT study

Background:Obesity has been inconsistently linked to prostate cancer, mainly with mortality rather than incidence. Few large-scale studies exist assessing obesity in relation to prostate-specific antigen (PSA)-detected prostate cancer.Methods:We used cases and stratum-matched controls from the population-based PSA-testing phase of the Prostate testing for cancer and Treatment study to examine the hypothesis that obesity as measured by body mass index (BMI), waist circumference and waist-to-hip ratio (WHR) is associated with increased prostate cancer risk, and with higher tumour stage and grade. In all, 2167 eligible cases and 11 638 randomly selected eligible controls with PSA values were recruited between 2001 and 2008. A maximum of 960 cases and 4156 controls had measurement data, and also complete data on age and family history, and were included in the final analysis. BMI was categorised as <25.0, 25.0–29.9, ⩾30.0 in kg m−2.Results:Following adjustment for age and family history of prostate cancer, we found little evidence that BMI was associated with total prostate cancer (odds ratio (OR): 0.83, 95% confidence interval (CI): 0.67, 1.03; highest vs lowest tertile; P-trend 0.1). A weak inverse association was evident for low-grade (OR: 0.76, 95% CI: 0.59, 0.97; highest vs lowest tertile; P-trend 0.045) prostate cancer. We found no association of either waist circumference (OR: 0.94, 95% CI: 0.80, 1.12; highest vs lowest tertile) or waist-to-hip ratio (WHR; OR: 0.93, 95% CI: 0.77, 1.11; highest vs lowest tertile) with total prostate cancer, and in analyses stratified by disease stage (all P-trend>0.35) or grade (all P-trend>0.16).Conclusion:General adiposity, as measured by BMI, was associated with a decreased risk of low-grade PSA-detected prostate cancer. However, effects were small and the confidence intervals had limits very close to one. Abdominal obesity (as measured by WHR/waist circumference) was not associated with PSA-detected prostate cancer.

Disproportionate Presentation of High Risk Prostate Cancer in a Safety Net Health System

Most prostate cancer research is based on relatively homogenous cohorts of men, often with comparatively high socioeconomic status. We describe prostate cancer characteristics in men treated in a public health system and hypothesize a disproportionate burden of high risk disease in this population. We created a clinical registry from a review of the medical records of 377 men diagnosed with prostate cancer in the San Francisco General Hospital system, which provides care to underserved, uninsured populations. We compared sociodemographic data and cancer characteristics with those in 2 large prostate cancer databases from a community (CaPSURE™) and an academic (University of California-San Francisco tumor registry) setting to assess differences in risk distribution using the D'Amico and Cancer of the Prostate Risk Assessment scoring systems. Compared to men in CaPSURE or the University of California-San Francisco tumor registry those in the San Francisco General Hospital cohort were nonwhite (76%), insured under Medicaid (31%) or uninsured (8%) and had adverse clinical characteristics, including median prostate specific antigen greater than 10 ng/ml at diagnosis and higher Gleason grade. In addition, the majority of patients (67%) had intermediate or high risk disease based on the D'Amico classification and a higher mean Cancer of the Prostate Risk Assessment score. Using ANOVA for continuous variables and the chi-square test for categorical variables, all comparisons were statistically significant (p <0.001). Men in the San Francisco General Hospital public health system bear a substantially higher burden of high risk disease that those in an academic or a community setting. Populations such as this would benefit most from targeted efforts for early detection and treatment to decrease prostate cancer morbidity and mortality.

Population‐based prostate‐specific antigen testing in the UK leads to a stage migration of prostate cancer

To determine, within the UK, the stage and grade of prostate cancers that would be found through population-based prostate specific antigen (PSA) testing and biopsy. In the 'Prostate Testing for Cancer and Treatment' trial (ProtecT), men aged 50-69 years were recruited from nine cities in the UK and from randomly selected practices of general practitioners. Those with a PSA level of >3 ng/mL were offered a prostate biopsy. Age, PSA, stage and grade at diagnosis of ProtecT participants with cancer were compared with contemporaneous incident cases aged 50-69 years (age-restricted Cancer Registry cases) registered with the Eastern Cancer Registration and Information Centre (ECRIC). Within ProtecT, 94,427 men agreed to be tested (50% of men contacted), 8807 ( approximately 9%) had a raised PSA level and 2022 (23%) had prostate cancer; 229 ( approximately 12%) had locally advanced (T3 or T4) or metastatic cancers, the rest having clinically localized (T1c or T2) disease. Within ECRIC, 12,661 cancers were recorded over the same period; 3714 were men aged 50-69 years at diagnosis. Men in ProtecT had a lower age distribution and PSA level, and the cancers were of lower stage and grade (P < 0.001 for all comparisons). If population-based PSA testing were introduced in the UK, approximately 2660 men per 100,000 aged 50-69 years would be found to have prostate cancer, compared to current rates of approximately 130 per 100,000. If half of men accepted PSA testing, approximately 160,000 cancers would be found, compared to 30,000 diagnosed each year at present. Population-based PSA testing resulted in a significant downward stage and grade migration, and most such cancers were of low stage and grade, which could lead to risks of over-treatment for some men.

Risk of dying from prostate cancer in men randomized to screening

Although the true benefits and disadvantages of prostate cancer screening are still not known, the analysis of fatal cases is important for increasing knowledge of the effects of prostate cancer screening on mortality. Who dies from prostate cancer despite participation in a population-based prostate-specific antigen (PSA) screening program? From the Goteborg branch of the European Randomized study of Screening for Prostate Cancer, 10,000 men randomly assigned to active PSA-screening every second year formed the basis of the present study. Prostate cancer mortality was attributed to whether the men were attendees in the screening program (attending at least once) or nonattendees. Thirty-nine men died from prostate cancer during the first 13 years. Both overall (34% vs 13 %; P<.0001) and cancer-specific mortality (0.8% vs 0.3 %; P<.005) were found to be significantly higher among nonattendees compared with attendees. Furthermore, the majority of deaths (12 of 18) among screening attendees were in men diagnosed at first screening (prevalent cases). Only 6 deaths (including 3 interval cases) were noted among men complying with the biennial screening program. Nonattendees in prostate cancer screening constitute a high-risk group for both death from prostate cancer and death from other causes comparable to that described in other cancer screening programs.

Prostate cancer mortality in screen and clinically detected prostate cancer: Estimating the screening benefit

BackgroundTo estimate the benefits of prostate-specific antigen (PSA) screening on prostate cancer (Pca) metastasis and Pca-specific mortality, we compared two populations with a well-defined difference in intensity of screening. MethodsBetween 1997 and 1999, a total of 11,970 men, aged 55–74years, were included in the intervention arm of the European Randomised Study of Screening for Prostate Cancer (ERSPC) section Rotterdam. Control population consisted of 133,287 men, aged 55–74years, between 1998 and 1999 in Northern Ireland (NI). Men were followed for Pca incidence, Pca metastasis and cause of death until 31st December 2006. ResultsMedian age in both groups was 63years at study entry (p=0.184). In Rotterdam 94.2% of men and in NI 6% of men underwent PSA testing. In Rotterdam, 1153 men (9.6%) were diagnosed with Pca with median baseline PSA of 5.1ng/ml. In NI, 3962 men (3.0%, p<0.001) were diagnosed with Pca with median baseline PSA of 18.0ng/ml (p<0.001). The relative risk of Pca metastasis during observation in the intervention population compared to control population was 0.47 (95% confidence interval (CI), 0.35–0.63; p<0.001). The relative risk of Pca-specific mortality was also lower in the intervention population compared to the control population after a median follow-up of 8.5years: 0.63 (95% CI, 0.45–0.88; p=0.008); absolute mortality reduction was 1.8 deaths per 1000 men. ConclusionsA relative reduction in Pca metastasis of 53% and Pca mortality of 37% was observed in the intervention population after 8.5years of observation. The impact of overdiagnosis, quality of life benefits and cost-effectiveness need to be assessed before population-based PSA screening can be recommended.

Measuring the psychosocial impact of population‐based prostate‐specific antigen testing for prostate cancer in the UK

To evaluate the psychosocial impact of participation in a population-based prostate-specific antigen (PSA) testing programme, akin to screening, and to explore the relationship between urinary symptoms reported before PSA testing and the response to the subsequent PSA result. This prospective questionnaire study was nested within the case-finding component of the ProtecT (prostate testing for cancer and treatment) feasibility study (ISRCTN20141297). Men aged 50-69 years from 18 general practices in three cities in the UK completed the Hospital Anxiety and Depression Scale (HADS), the Short Form-12 (SF-12) Health Survey, and the International Continence Society 'male' (ICSmale) questionnaires before giving consent for a PSA test in a community clinic (baseline). Men with an 'abnormal' PSA result returned for further investigation (including biopsy) and repeated these questionnaires before biopsy. At baseline, study participants had similar levels of anxiety and depression to the general male population. There was no increase in the HADS scores, or reduction in the SF-12 mental health component summary score, on attendance at the biopsy clinic after receiving an 'abnormal' PSA result. Urinary symptoms were associated with levels of anxiety and depression before receiving a PSA result (baseline), but were not associated with anxiety and depression at biopsy independently of baseline scores. Therefore changes in anxiety or depression at biopsy did not appear to differ between those with and without urinary symptoms. This study confirms the findings of other studies that the deleterious effects of receiving an abnormal PSA result during population screening are not identified by generic health-status questionnaires. Comparisons with outcomes of studies measuring cancer-specific distress and using qualitative research methods raise the question of whether a prostate cancer screening-specific instrument is required. However, a standardized measure of anxiety identified differences at baseline between those who did and did not report urinary symptoms. These findings suggest that it might be advisable to better inform men undergoing PSA testing about the uncertain relationship between urinary symptoms and prostate cancer, to minimize baseline levels of psychological distress.

Cancer surveillance series: interpreting trends in prostate cancer--part III: Quantifying the link between population prostate-specific antigen testing and recent declines in prostate cancer mortality.

The objective of this study was to investigate the circumstances under which dissemination of prostate-specific antigen (PSA) testing, beginning in 1988, could plausibly explain the declines in prostate cancer mortality observed from 1992 through 1994. We developed a computer simulation model by use of information on population-based PSA testing patterns, cancer detection rates, average lead time (the time by which diagnosis is advanced by screening), and projected decreased risk of death associated with early diagnosis of prostate cancer through PSA testing. The model provides estimates of the number of deaths prevented by PSA testing for the 7-year period from 1988 through 1994 and projects what prostate cancer mortality for these years would have been in the absence of PSA testing. Results were generated by assuming a level of screening efficacy similar to that hypothesized for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Under this assumption, the projected mortality in the absence of PSA testing continued the increasing trend observed before 1991 only when it was assumed that the mean lead time was 3 years or less. Projected mortality trends in the absence of PSA screening were not consistent with pre-1991 increasing trends for lead times of 5 years and 7 years. When screening is assumed to be at least as efficacious as hypothesized in the PLCO trial, it is unlikely that the entire decline in prostate cancer mortality can be explained by PSA testing based on current beliefs concerning lead time. Only very short lead times would produce a decline in mortality of the magnitude that has been observed.