Population-based Prostate Cancer Screening Research Articles

1034 An update on the outcome of men on active surveillance in the Gothenburg randomized population-based prostate cancer screening trial

1034 An update on the outcome of men on active surveillance in the Gothenburg randomized population-based prostate cancer screening trial

Opportunistic Testing Versus Organized Prostate-specific Antigen Screening: Outcome After 18 Years in the Göteborg Randomized Population-based Prostate Cancer Screening Trial

BackgroundIt has been shown that organized screening decreases prostate cancer (PC) mortality, but the effect of opportunistic screening is largely unknown. ObjectiveTo compare the ability to reduce PC mortality and the risk of overdiagnosis between organized and opportunistic screening. Design, setting, and participantsThe Göteborg screening study invited 10 000 randomly selected men for prostate-specific antigen (PSA) testing every 2 yr since 1995, with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml. The control group of 10 000 men not invited has been exposed to a previously reported increased rate of opportunistic PSA testing. Both groups were followed until December 31, 2012. Outcome measurements and statistical analysisObserved cumulative PC incidence and mortality rates in both groups were calculated using the actuarial method. Using historical data from 1990–1994 (pre-PSA era), we calculated expected PC incidence and mortality rates in the absence of any PSA testing. The number needed to invite (NNI) and the number needed to diagnose (NND) were calculated by comparing the expected versus observed incidence and mortality rates. Results and limitationsAt 18 yr, 1396 men were diagnosed with PC and 79 men died of PC in the screening group, compared to 962 and 122, respectively, in the control group. In the screening group, the observed cumulative PC incidence/mortality was 16%/0.98% compared to expected values of 6.8%/1.7%. The corresponding values for the control group were 11%/1.5% and 6.9%/1.7%. Organized screening was associated with an absolute PC-specific mortality reduction of 0.72% (95% confidence interval [CI] 0.50–0.94%) and relative risk reduction of 42% (95% CI 28–54%). There was an absolute reduction in PC deaths of 0.20% (95% CI –0.06% to 0.47%) and a relative risk reduction of 12% (95% CI –5 to 26%) associated with opportunistic PSA testing. NNI and NND were 139 (95% CI 107–200) and 13 for organized biennial screening and 493 (95% CI 213– −1563) and 23 for opportunistic screening. The extent of opportunistic screening could not be measured; incidence trends were used as a proxy. ConclusionsOrganized screening reduces PC mortality but is associated with overdiagnosis. Opportunistic PSA testing had little if any effect on PC mortality and resulted in more overdiagnosis, with almost twice the number of men needed to be diagnosed to save one man from dying from PC compared to men offered an organized biennial screening program. Patient summaryProstate-specific antigen (PSA) screening within the framework of an organized program seems more effective than unorganized screening.

Cumulative probability of prostate cancer detection using the international prostate symptom score in a prostate-specific antigen-based population screening program in Japan.

The International Prostate Symptom Score (IPSS) is often used as an interview sheet for assessing lower urinary tract symptoms (LUTS) at the time of prostate-specific antigen (PSA) testing during population-based screening for prostate cancer. However, the relationship between prostate cancer detection and LUTS status remains controversial. To elucidate this relationship, the cumulative probability of prostate cancer detection using IPSS in biopsy samples from patients categorized by serum PSA levels was investigated. The clinical characteristics of prostate cancer detected using IPSS during screening were also investigated. A total of 1,739 men aged 54-75 years with elevated serum PSA levels who completed the IPSS questionnaire during the initial population screening in Kanazawa City, Japan and underwent systematic transrectal ultrasonography-guided prostate biopsy between 2000 and 2013 were enrolled in the present study. Of the 1,739 men, 544 (31.3%) were diagnosed with prostate cancer during the observation period. The probability of cancer detection at 3 years in the entire study population was 27.4% and 32.7% for men with IPSS ≤ 7 and those with IPSS ≥ 8, respectively; there was no statistically significant difference between groups. In men with serum PSA levels of 6.1 to 12.0 ng/ mL at initial screening, the probability of cancer detection was significantly higher in men with IPSS ≤ 7 than in those with IPSS ≥ 8. There were no significant differences in clinical characteristics between groups of patients stratified by IPSS. These findings indicate that the use of IPSS for LUTS status evaluation may be useful for prostate cancer detection in the limited range of serum PSA levels.

850 A comparison of the effectiveness of organised versus opportunistic screening measured as number need to invite (NNI) and number needed to diagnose (NND). Results from the Gothenburg randomised population-based prostate cancer screening trial

850 A comparison of the effectiveness of organised versus opportunistic screening measured as number need to invite (NNI) and number needed to diagnose (NND). Results from the Gothenburg randomised population-based prostate cancer screening trial

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Impacts of a population-based prostate cancer screening programme on excess total mortality rates in men with prostate cancer: a randomized controlled trial

To assess the effect of screening in terms of excess mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). A total of 141,578 men aged 55–69 were randomized to systematic screening or usual care in ERSPC sections in Finland, Italy, the Netherlands and Sweden. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC)patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a diagnosis with PC adjusted for study centre,study arm and study attendance. The excess mortality rates were compared between the two study arms. The PC incidence was 9.25 per 1000 person-years in the intervention arm and 5.49 per 1000 person-years in the control arm, relative risk (RR) 1.69 (95% confidence interval [CI]1.62–1.76). The excess mortality among men with PC was 0.29 per 1000 person-years in the intervention arm and 0.37 per 1000 person-years in the control arm; the RR for excess mortality was 0.77 (95% CI 0.55–1.08). The absolute risk reduction in the excess mortality was 0.08 per 1000 person-years. The overall mortality was not significantly different between the intervention and the control arms of the study: RR 0.99 (95% CI 0.96–1.01). Although the reduction in excess mortality was not statistically significant, the between arm reduction in excess mortality rate was in line with the previously reported 20% reduction in the disease-specific mortality. This finding indicates that the reduction in PC mortality in the ERSPC trial cannot be due to a bias in cause of death adjudication.

Impacts of a population-based prostate cancer screening programme on excess total mortality rates in men with prostate cancer: a randomized controlled trial.

Objectives To assess the effect of screening in terms of excess mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). Methods A total of 141,578 men aged 55-69 were randomized to systematic screening or usual care in ERSPC sections in Finland, Italy, the Netherlands and Sweden. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC) patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a diagnosis with PC adjusted for study centre, study arm and study attendance. The excess mortality rates were compared between the two study arms. Results The PC incidence was 9.25 per 1000 person-years in the intervention arm and 5.49 per 1000 person-years in the control arm, relative risk (RR) 1.69 (95% confidence interval [CI] 1.62-1.76). The excess mortality among men with PC was 0.29 per 1000 person-years in the intervention arm and 0.37 per 1000 person-years in the control arm; the RR for excess mortality was 0.77 (95% CI 0.55-1.08). The absolute risk reduction in the excess mortality was 0.08 per 1000 person-years. The overall mortality was not significantly different between the intervention and the control arms of the study: RR 0.99 (95% CI 0.96-1.01). Conclusions Although the reduction in excess mortality was not statistically significant, the between-arm reduction in excess mortality rate was in line with the previously reported 20% reduction in the disease-specific mortality. This finding indicates that the reduction in PC mortality in the ERSPC trial cannot be due to a bias in cause of death adjudication.

Outcome Following Active Surveillance of Men with Screen-detected Prostate Cancer. Results from the Göteborg Randomised Population-based Prostate Cancer Screening Trial

BackgroundActive surveillance (AS) has emerged as a treatment strategy for reducing overtreatment of screen-detected, low-risk prostate cancer (PCa). ObjectiveTo assess outcomes following AS of men with screen-detected PCa. Design, setting, and participantsOf the 968 men who were diagnosed with screen-detected PCa between 1995 and 2010 in the Göteborg randomised, population-based PCa screening trial, 439 were managed with AS and were included in this study. Median age at diagnosis was 65.4 yr of age, and median follow-up was 6.0 yr from diagnosis. InterventionThe study participants were followed at intervals of 3–12 mo and were recommended to switch to deferred active treatment in case of a progression in prostate-specific antigen, grade, or stage. Outcome measurements and statistical analysisThe end points—overall survival (OS), treatment-free survival, failure-free (no relapse after radical treatment) survival, and cancer-specific survival—were calculated for various risk groups (very low, low, intermediate, and high) with Kaplan-Meier estimates. A Cox proportional hazards model as well as a competing risk analysis were used to assess whether risk group or age at diagnosis was associated with failure after AS. Results and limitationsForty-five per cent of all screen-detected PCa were managed with AS, and very low-risk and low-risk PCa constituted 60% of all screen-detected PCa. Thirty-seven per cent (162 of 439) switched from surveillance to deferred active treatment, and 39 men failed AS. The 10-yr OS, treatment-free survival, and failure-free survival were 81.1%, 45.4%, and 86.4%, respectively (Kaplan-Meier estimates). Men with low-, intermediate-, and high-risk tumours had a hazard ratio for failure of 2.1 (p=0.09), 3.6 (p=0.002), and 4.6 (p=0.15), respectively, compared to very low-risk tumours (Cox regression). Only one PCa death occurred, and one patient developed metastasis (both in the intermediate-risk group). The main limitation of this study is the relatively short follow-up. ConclusionsA large proportion of men with screen-detected PCa can be managed with AS. AS appears safe for men with low-risk PCa.

Population-based screening in the era of genomics.

To date, risk profiles based on the known common susceptibility variants have limited value in predicting risk of disease but they could be used for risk stratification in prevention programmes at population level. We illustrate the potential utility of polygenic risk stratification using the case of population-based screening for prostate and breast cancer. We compared the number of individuals eligible for screening and the number of cases potentially detectable by screening in a population undergoing screening based on age alone with a population undergoing stratified screening based on age and polygenic risk profile. Stratified screening strategy based on age and genetic risk would potentially improve the efficiency of screening programmes and reduce their adverse consequences. Organisational, ethical, legal and social issues need to be addressed before stratified screening programmes could be implemented.

Prostate-specific antigen (PSA) screening in the United States: Patterns of use and PSA outcomes in screened versus unscreened men.

4658 Background: PSA screening is a subject of substantial controversy. We examined patterns of PSA screening using a recent cohort from the population-based National Health and Nutrition Examination Survey (NHANES) study and compared PSA levels of previously screened vs. never screened men. Methods: NHANES is a cross-sectional study which collects health-related information (including cancer screening history, family history and socioeconomic variables) and blood samples from nationally representative samples of the US population. We included 2,078 previously screened men and 1,902 never screened men surveyed from 2003-8. Statistical analysis accounted for sampling weights. Results: 25% of men age 40-49 years had prior PSA screening; 56% age 50-59, and 72% age 60-69. Screening rates were higher for men with family history (68% vs. 50% no history, p<.001), health insurance (58% vs. 21% no insurance, p<.001), and Caucasians (59% vs. 44% non-Caucasian, p<.001). No significant differences were seen in the PSA values of screened vs. never screened men stratified by age (Table), or by race/ethnicity, insurance status, or family history. Conclusions: Rates of PSA screening in the US differ by age, family history, race/ethnicity and insurance status. However, no significant differences were seen in PSA values of screened vs. unscreened men, and very few patients under 60 years of age had PSA values ≥10. Despite questions about the appropriate role of PSA testing, population-based prostate cancer screening is routinely conducted among Caucasian and non-Caucasian men 50 years of age and older. [Table: see text]

The absence of voiding symptoms in men with a prostate‐specific antigen (PSA) concentration of ≥3.0 ng/mL is an independent risk factor for prostate cancer: results from the Gothenburg Randomized Screening Trial

What's known on the subject? and What does the study add? There are only a few studies and no consensus concerning the relationship between LUTS and prostate cancer. This paper focuses on 2353 men with an elevated PSA level within the Gothenburg Randomized Screening Trial who underwent biopsy and answered questions regarding LUTS. The main conclusion was that the absence of voiding symptoms is an independent risk factor for prostate cancer detection. To investigate whether men with obstructive voiding symptoms are at increased risk for being diagnosed with prostate cancer within the Gothenburg randomized population-based prostate cancer screening trial. In 1995, 20 000 men born between 1930 and 1944 were randomly selected from the population register and randomized to either a screening group (10 000), invited for total prostate-specific antigen (tPSA) testing every second year until they reached an upper age-limit pending between 67 and 71 years, or to a control group not invited (10 000). Men with a PSA concentration of ≥3.0 ng/mL were offered further examination with prostate biopsies. Immediately before the physician's examination a self-administered, study-specific questionnaire was completed including one question concerning obstructive voiding symptoms. Multivariate logistic regression modelling was used to estimate odds ratios (ORs) for associations of age, tPSA, free/total PSA (f/tPSA) ratio, prostate volume and the presence of voiding symptoms in prostate cancer risk. A P < 0.05 was considered statistically significant. Between 1995 and 2010 there were 2590 men who had an elevated PSA concentration (≥3.0 ng/mL) at least once during the study. Of these, 2353 men (91%) accepted further clinical examination with transrectal ultrasonography (TRUS) and prostate biopsies. In all, 633/2353 men had prostate cancer (27%) on biopsy and 1720/2353 men (73%) had a benign pathology. Men with prostate cancer reported a lower frequency of voiding symptoms (24% vs 31%, P < 0.001), independent of age and locally advanced tumours (T2b-T4). In the multivariate logistic regression model increasing age and tPSA were positively associated with prostate cancer while prostate volume, f/tPSA ratio and the presence of voiding symptoms were all inversely associated with the risk of detecting prostate cancer in a screening setting. This inverse association of voiding symptoms and prostate cancer detection was restricted to men with large prostates (>37.8 mL); 15% in men with voiding symptoms vs 22% in asymptomatic men (P < 0.001). The presence of voiding symptoms should not be a decision tool for deciding which men with an elevated PSA concentration should be offered biopsies of the prostate.

1094 Outcome following surveillance of men with screen-detected prostate cancer. Results from the Gothenburg randomised population-based prostate cancer screening trial

1094 Outcome following surveillance of men with screen-detected prostate cancer. Results from the Gothenburg randomised population-based prostate cancer screening trial

High accuracy of Swedish death certificates in men participating in screening for prostate cancer: A comparative study of official death certificates with a cause of death committee using a standardized algorithm

Recently, the first mortality data from the Göteborg Randomized Population-based Prostate Cancer Screening Trial showed a 44% reduction in prostate cancer (PC)-specific mortality as a result of screening with prostate-specific antigen (PSA). As death of PC is the main endpoint, an accurate determination of the cause of death (COD) is crucial. The aim of this study was therefore to investigate the accuracy of death certificates of men in the Göteborg Randomized Population-based Prostate Cancer Screening Trial. Men with a PC diagnosis and who died within the study period (1995-2008) were included. Relevant medical information, including death certificate, was collected. An independent COD committee reviewed the material following a flowchart to classify the COD. The committee's decision was compared with the COD on the death certificate. Of the 285 men included in the study, 278 men were eligible for a comparative analysis. The committee and the death certificates agreed on PC as the underlying COD in 116 men and causes other than PC in 151. There were 11 discordant cases, for an overall agreement of 96%. Men with PC in the screening group had, compared with the control group, a significantly lower PC-specific mortality but did not differ in non-PC-specific mortality. This study concludes that Swedish death certificates are of high accuracy and can be used for endpoint evaluation in screening studies for PC.

The excess burden of side-effects from treatment in men allocated to screening for prostate cancer. The Göteborg randomised population-based prostate cancer screening trial

Background The number of men needed to treat to prevent one death is rather high in prostate cancer screening. How this affects the burden of treatment-related side-effects is unclear. The aim of this study was to evaluate the treatment related morbidity following radical prostatectomy in men participating in the Göteborg randomised population-based prostate cancer screening trial. Methods In 1995, 20,000 men aged 50–64 years were randomly allocated (1:1) to biennial PSA-screening or to a control group not invited. A subset of prostate cancer patients undergoing radical prostatectomy between 2001 and 2008 responded to questionnaires preoperatively and at 18 months postoperatively. The primary endpoint was patient-reported frequencies of erectile dysfunction as measured by the validated International Index of Erectile Function-5 questionnaire and urinary incontinence as assessed by use of pads. Analyses were made according to intention to screen. Findings After 14 years of follow-up, a total of 1849 men were detected with prostate cancer (1138 screened versus 711 controls, excluding 7 cancers detected at autopsy in the control group). Overall, 1047 received treatment with curative intent and radical prostatectomy was performed in 829 cases (79.2%). In this study, 294 of these men participated (205 screened and 89 controls). Of preoperatively potent men 79.1% (91/115) in the screening-group and 90.7% (49/54) in the control-group became impotent or sexually inactive 18 months postoperatively, whereas 14.3% (29/203) of screened men and 20.5% (18/88) of controls were considered postoperatively incontinent (regular use of pads). Extrapolated data yields that 120/10,000 more men become impotent and 25/10,000 more men will have the need of pads among men invited to regular PSA screening. The ‘cost’ per life saved at the same follow-up of screening is four men impotent and less than one man incontinent. Interpretation Despite the relatively high risk of erectile dysfunction and incontinence following radical prostatectomy for prostate cancer, the excess burden of permanent side-effects after population-based screening can be regarded as relatively low, when related to the number of men saved from prostate cancer death. These data can be useful when calculating the harms and benefits of screening. However, the outcome on a population-level may differ from the benefit for the individual.

Should prostate-specific antigen screening be offered to asymptomatic men?

The benefits of population-based prostate cancer screening are the detection of clinically important prostate cancers at an early, still curable, stage and the subsequent reduction of prostate cancer-specific mortality. However, a prostate-specific antigen (PSA)-based prostate cancer screening program is currently insufficient to warrant its introduction as a public health policy. The main reasons are insufficient knowledge regarding the optimal screening strategy and overdiagnosis and overtreatment of indolent prostate cancers that are unlikely to lead to complaints or death. In some countries, guidelines have been developed on screening for prostate cancer, but the diversity of recommendations illustrates the limited knowledge on the optimal strategy. Therefore, men should be well informed about the benefits and potential harms of PSA screening in order to enable them to make an informed decision. Although a mortality reduction can be achieved by early detection of prostate cancer, patients and physicians must be aware of the current side effects of screening. Algorithms that advise screening at a young age (<55 years), with screening intervals of less than 4 years and low PSA thresholds (<3 ng/ml) for prostate biopsy seem premature and are not supported by evidence.

Effect of the correction for noncompliance and contamination on the estimated reduction of metastatic prostate cancer within a randomized screening trial (ERSPC section Rotterdam)

The European Randomized study of Screening for Prostate Cancer (ERSPC) has recently reported a 20% reduction in death from prostate cancer in a population-based prostate cancer screening (core age group: 55-69 years of age). The effect of screening may be diluted by noncompliance in the screening arm and contamination by PSA testing in the control arm. The purpose is to analyze the effect of prostate cancer screening on the incidence of metastatic prostate cancer, both with and without adjustment for noncompliance and contamination. We analyzed the occurrence of metastases in 42,376 men aged 55-75 years who were randomized in the Rotterdam section of the ERSPC between 1993 and 1999. Contamination adjustment was based on follow-up findings and questionnaire data from all men in the control group who developed prostate cancer and from a random sample of 291 men without cancer who had a PSA test. Prostate cancer screening significantly reduced the occurrence of metastatic prostate cancer in the intention-to-screen analysis [RR 0.75, 95% CI 0.59-0.95, p = 0.02] and more so in adjusted analyses; contamination adjusted RR 0.73, 95% CI 0.56-0.96; noncompliance adjusted RR 0.72, 95% CI 0.55-0.95 and fully adjusted analysis RR 0.68, 95% CI 0.49-0.94, p = 0.02. In the population of ERSPC Rotterdam (N = 42,376 men), screening reduces the risk to be diagnosed with metastatic prostate cancer considerably on population level, an effect which is even more pronounced in men who are in fact screened.

Rethinking Screening for Breast Cancer and Prostate Cancer

Population-based screening for prostate and breast cancer has been advocated on the assumption that their early detection and treatment will reduce disease-associated morbidity and mortality. A high proportion of the US population is screened regularly and in the last 2 decades, screening has nearly doubled the detection of early breast and prostate cancer. The overall incidence of both of these tumors has increased substantially and remains higher than prescreening levels. Current screening methods have not resulted in the expected reduction in mortality of either of these tumors. Suggested reasons for the lack of a greater impact on mortality include the following: screening appears to increase the detection of slow-growing early indolent cancers that pose minimal risk. Such tumors are probably cured by surgery alone. Overdetection and overtreatment of such minimal-risk cancers subjects patients unnecessarily to morbidity from adjunct therapy and markedly increase the cost of therapy. Screening also may miss a high proportion of fast-growing aggressive or advanced tumors because they are not screened with sufficient frequency for detection and cure. The authors believe that new diagnostic tests and screening methods must be developed to distinguish between minimal risk and high-risk tumors in order to make a substantial impact on patient survival and reduce the burden of treatment on patients and society.

15-Year Followup of a Population Based Prostate Cancer Screening Study

15-Year Followup of a Population Based Prostate Cancer Screening Study

Informed decision making on PSA testing for the detection of prostate cancer: An evaluation of a leaflet with risk indicator

Background Population-based screening for prostate cancer (PCa) remains controversial. To help men making informed decisions about prostate specific antigen (PSA) screening a risk indicator ( www.uroweb.org) was developed. This risk indicator is embedded in a leaflet that informs men about the pros and cons of PCa screening and enables calculation of the individual risk of having a biopsy detectable PCa. Aim To assess the effect of providing a leaflet including individualized risk estimation on informed decision making of men, i.e. knowledge about PCa and PSA screening, attitude towards undergoing a PSA test and intention to have a PSA test. Methods An intervention study among 2000 men, aged 55–65 years, randomly selected from the population registry of the city of Dordrecht, the Netherlands, in 2008. Men were sent a questionnaire on knowledge of PCa, attitude and intention to have a PSA test. Men without a history of (screening for) PCa were sent the leaflet and Questionnaire 2 within 2 weeks after returning Questionnaire 1. Validated health and anxiety measures were used. Results One thousand and twenty seven of 2000 men completed Questionnaire 1 (51%), of whom 298 were excluded due to a history of (screening for) PCa. Of the 729 remaining men, 601 completed Questionnaire 2 as well. At the second assessment significantly more men met the requirements of informed decision making (15% versus 33%, p < 0.001), more men had relevant knowledge (284/601, 50% versus 420/601, 77%, p < 0.001) and the intention to have a PSA test had increased ( p < 0.001). Conclusions Providing information on PCa screening combined with individualized risk estimation enhanced informed decision making and may be used for shared decision making on PSA screening of physicians and patients.

Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases

BackgroundProstate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico.MethodsAfter receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB).ResultsA total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores ≥ 7.ConclusionOur results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason ≥ 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns.