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.

BACKGROUND: The 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. OBJECTIVE: To 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 PARTICIPANTS: We 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 ANALYSIS: We 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 LIMITATIONS: The 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. CONCLUSIONS: In 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 SUMMARY: In 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.

Intervention-related Deaths in the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. OBJECTIVE: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). DESIGN SETTING AND PARTICIPANTS: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55-69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. RESULTS AND LIMITATIONS: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99-1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. CONCLUSIONS: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. PATIENT SUMMARY: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.

A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer.

BACKGROUND: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. OBJECTIVE: To determine whether PSA screening decreases PCa mortality for up to 16yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. DESIGN, SETTING, AND PARTICIPANTS: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182160 men, followed up until 2014 (maximum of 16yr), with a predefined core age group of 162389 men (55-69yr), selected from population registry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. RESULTS AND LIMITATIONS: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p<0.001) at 16yr. The difference in absolute PCa mortality increased from 0.14% at 13yr to 0.18% at 16yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16yr compared with 742 at 13yr. The number needed to diagnose was reduced to 18 from 26 at 13yr. Men with PCa detected during the first round had a higher prevalence of PSA >20ng/ml (9.9% compared with 4.1% in the second round, p<0.001) and higher PCa mortality (hazard ratio=1.86, p<0.001) than those detected subsequently. CONCLUSIONS: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level. PATIENT SUMMARY: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer.

The efficacy of prostate-specific antigen screening: Impact of key components in the ERSPC and PLCO trials.

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates. METHODS: The authors calibrated 2 microsimulation models to individual-level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step-by-step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials. RESULTS: Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0. CONCLUSIONS: The observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197-206. © 2017 American Cancer Society.

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials.

BACKGROUND: The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction. OBJECTIVE: To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO. DESIGN: Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models. SETTING: Randomized controlled trials in Europe and the United States. PARTICIPANTS: Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization. INTERVENTION: Prostate cancer screening. MEASUREMENTS: Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began. RESULTS: Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening. LIMITATION: The MLT is a simple metric of screening and diagnostic work-up. CONCLUSION: After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality. PRIMARY FUNDING SOURCE: National Cancer Institute.

Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by Center within the European Randomized Study of Prostate Cancer Screening.

PURPOSE: The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening (ERSPC). EXPERIMENTAL DESIGN: We analyzed the absolute mortality reduction expressed as number needed to invite (NNI = 1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO = 1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. RESULTS: Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI, 200-7,000 and NNO, 16-69. Extent of overdiagnosis and mortality reduction was closely associated [correlation coefficient, r = 0.76; weighted linear regression coefficient, ß = 33; 95% confidence interval (CI), 5-62; R(2) = 0.72]. For an averted prostate cancer death at 13 years of follow-up, 12 to 36 excess cases had to be detected in various centers. CONCLUSIONS: The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear.

Metastatic Prostate Cancer Incidence and Prostate-specific Antigen Testing: New Insights from the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality. DESIGN, SETTING, AND PARTICIPANTS: Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis. RESULTS AND LIMITATIONS: In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03-2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16-1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89-1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52-0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller. CONCLUSIONS: The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr. PATIENT SUMMARY: The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer.

[Definition and stabilization of processes I. Management processes and support in a Urology Department]. / Definición y estabilización de los procesos I. Procesos de gestión y soporte en un Servicio de Urología.

The implantation of total quality management models in clinical departments can better adapt to the 2009 ISO 9004 model. An essential part of implantation of these models is the establishment of processes and their stabilization. There are four types of processes: key, management, support and operative (clinical). Management processes have four parts: process stabilization form, process procedures form, medical activities cost estimation form and, process flow chart. In this paper we will detail the creation of an essential process in a surgical department, such as the process of management of the surgery waiting list.

[Inverse innovation models in the nurse clinic of a Urology Department]. / Modelo de innovación inversa en la consulta de enfermería de Servicios de Urología.

OBJECTIVES: In the urology clinics there is an important volume of limited-complexity pathology that consumes an important part of resources. Delegating some tasks of this type to Nurses may imply a competitive advantage in economic terms without decrease in the quality of the care given to patients and their level of satisfaction. This is an example of the concept of inverse innovation. In this work we try to make public our experience in the management by nursing staff of features of the urology consultation traditionally reserved to physicians, as well as the design of the related processes. METHODS: We developed the most frequent processes competence of the nursing staff in the unit: 1) Care of ambulatory urological surgery pathology; 2) Urologic ultrasound; 3) Traditional urologic nurse consultation. RESULTS: During 2013 the nursing staff performed 423 ambulatory urologic surgery pathology clinic visits, 931 urologic ultrasounds and 1019 varied actions corresponding to traditional urological nurse work.We developed stabilization formularies and flow diagrams of the aforementioned processes. We performed a quantification of the amount of money saved in comparison with the costs generated if a nurse or a physician was employed. Such saving was 2,78 and 4,00 Euros in the ambulatory urological surgery pathology and urologic ultrasound, respectively. Total savings in both processes was 4900 Euros. CONCLUSIONS: Implication of urological nursing staff in certain care tasks traditionally reserved to the physician is possible without increase in quality defects, obtaining an advantage in terms of economic cost and flexibility in staff organization thanks to the expansion of the competence array.

Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.

BACKGROUND: The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. METHODS: ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. FINDINGS: With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88). INTERPRETATION: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. FUNDING: Each centre had its own funding responsibility.

Outpatient urologic surgery office conducted by nursing staff. A process integrated in a total quality strategy.

OBJECTIVES: To create an innovative process to care for urological outpatient surgery patients in an outpatient clinic basis conducted by nursing staff. METHODS: Our centre covers a population of 153,266 inhabitants. A differentiated process for urological outpatient surgery patients has been implemented, conducted by nursing staff trained for the attendance of urologic patients ("phimosis","short penile frenulum",and "vasectomy request" sent from Primary Care units). Planning and implementation phases have been carried out. In the control phase, a questionnaire was given after surgical procedures with 9 different items, in order to assess different issues of the process. RESULTS: A total of 224 patients were attended during the study period, and 175 valid questionnaires were collected (78.1%). The procedures performed were circumcision (11.7%), frenuloplasty (14.6%), and vasectomy (73.7%), with a median patient age of 36 years. Satisfaction level was high for all items of the questionnaire, with 98.2% of patients" very satisfied" or "rather satisfied" when asked for the overall quality of attention of the whole process. The lowest scores were obtained in items that assessed delay from the appointment to attendance date (5.1% of patients "little satisfaction or not satisfied"), and the perception of information supplied (2.3% "little satisfaction or not satisfied"). A lower satisfaction score was observed (in the delay from appointment to attendance) in younger patients (p=0.001) and in patients who underwent circumcision (p=0.004). No complaints with regard to this process were collected. No incorrect indications for interventions were observed. CONCLUSIONS: The attendance of urological outpatient surgery patients can be safely and effectively performed by nursing staff trained for the care of urologic patients, without observing a decrease of the level of user satisfaction. Focusing on a process strategy allows the identification of areas for improvement and makes possible total quality management.

Prostate-cancer mortality at 11 years of follow-up.

BACKGROUND: Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up. METHODS: The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer. RESULTS: After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality. CONCLUSIONS: Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).

The performance of vasectomy in an urban municipality. Practical considerations for follow-up.

OBJECTIVES: To establish an adequate follow-up protocol based on time to azoospermia achievement after vasectomy. Also, to review the rate of complications in our setting. METHODS: Retrospective analysis of 391 men who underwent vasectomy. Follow-up was performed by means of semen analysis 6 months after surgery, and then every 3 months until azoospermia was achieved. Data of visits to the emergency unit at our centre were obtained within the first 30 postoperative days. RESULTS: During follow-up 567 semen analysis were performed. From 391 vasectomy interventions, 275 had at least one semen sample available and valid for processing. After the first 6 months from surgery, 41.1%men still presented nonmotile rare sperm in semen analysis, 9.7% after 9 months, and 4.7% after 12 months. If semen analysis was postponed from 6 to 9 months after surgery, a total yearly saving of 6,153.23 Euro would be observed in our setting, but with the drawback of delaying the diagnosis of azoospermia in nearly 60% of men. Overall complication rate was 3.1%(only one man required hospital admittance and reintervention). No statistical difference was observed in operative time with regard to the presence or absence of urological complications. CONCLUSIONS: The percentage of men not achieving azoospermia 6 months after surgery is notorious. Vasectomy practice in our setting seems to be reliable and safe, with a limited rate of complications.

The effect of study arm on prostate cancer treatment in the large screening trial ERSPC.

Prostate cancer (PC) mortality is the most valid end-point in screening trials, but could be influenced by the choice of initial treatment if treatment has an effect on mortality. In this study, PC treatment was compared between the screening and control arms in a screening trial. Data were collected from the European Randomized Study of Screening for Prostate Cancer (ERSPC). The characteristics and initial treatment of PC cases detected in the screening and the control arm were compared. Polytomous logistic regression analysis was used to assess the influence of study arm on treatment, adjusting for potential confounders and with statistical imputation of missing values. A total of 8,389 PC cases were detected, 5,422 in the screening arm and 3,145 in the control arm. Polytomous regression showed that trial arm was associated with treatment choice after correction for missing values, especially in men with high-risk PC. A control subject with high-risk PC was more likely than a screen subject to receive radiotherapy (OR: 1.43, 95% CI: 1.01-2.05, p = 0.047), expectant management (OR: 2.92, 95% CI: 1.33-6.42, p = 0.007) or hormonal treatment (OR: 1.77, 95% CI: 1.07-2.94, p = 0.026) instead of radical prostatectomy. However, trial arm had only a minor role in treatment choice compared to other variables. In conclusion, a small effect of trial arm on treatment choice was seen, particularly in men with high-risk PC. Therefore, differences in treatment between arms are unlikely to play a major role in the interpretation of the results of the ERSPC.

Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC).

BACKGROUND: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. OBJECTIVE: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. DESIGN, SETTING, AND PARTICIPANTS: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). INTERVENTION: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. MEASUREMENTS: Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. RESULTS AND LIMITATIONS: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. CONCLUSIONS: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.

Screening and prostate-cancer mortality in a randomized European study.

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer. METHODS: We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006. RESULTS: In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90). CONCLUSIONS: PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)

Extent of prostate-specific antigen contamination in the Spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

OBJECTIVES: The performance of tests outside prostate cancer screening trials (PSA contamination) may affect their statistical power. The present study addressed the extent of PSA contamination in the Spanish section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) and its impact on biopsy performance and prostate cancer detection. METHODS: Data linkage was performed to address screening-related interventions outside the study. Four databases were used: (1) Spanish ERSPC database (n=4278), (2) laboratory database with all PSA determinations (n=31,140), (3) database of 1608 prostate biopsies, and (4) records of all prostate cancers (n=819) diagnosed at our centre. PSA contamination, biopsy performance, and cancer detection rates were calculated. RESULTS: Median follow-up time was 6.6 yr. A total of 2201 PSA determinations were performed for 1253 men. Cumulative PSA contamination was 29.3% (17% in the control arm during the first 4 yr). A higher proportion of men undergoing biopsies was found in the screening arm (21.3% vs. 2.9% in the control arm, p<0.0001). Similarly, higher cancer detection rates were found in the screening (4.7% vs. 1.2% in the control arm, p<0.0001). CONCLUSIONS: In our experience, the PSA contamination rate has increased during the last years, but its impact on biopsy performance and cancer detection in the control arm of the trial is limited and not likely to compromise the statistical power of the ERSPC trial.

Prostate cancer detection is also relevant in low prostate specific antigen ranges.

OBJECTIVE: To address detection rates and clinical features of the cancers detected with low prostate specific antigen (PSA) levels. METHODS: In the context of a prostate cancer (PCa) screening program 1097 men attended to a new rescreen round. Sextant prostate biopsy was recommended when PSA > or =3 ng/ml. We also recommended to undergo biopsy in the range 1.0-2.99 ng/ml when free to total (f/t) PSA ratio < or =20%. Detection rate was calculated and clinical features of the cancers detected were studied. RESULTS: Mean age was 61.1 years. A total of 497 (45.3%) had total PSA <1.0 ng/ml, 439 (40%) between 1.0 and 2.99 ng/ml, and 161 (14.7%) > or =3.0 ng/ml. In the group with PSA between 1.0 and 2.99 ng/ml and f/t PSA ratio < or =20% a total of 249 biopsies were indicated (159 performed, acceptance 63.9%), and 15 cancers detected (detection rate 9.4%). Biopsy was recommended to 72 men with PSA between 3.0 and 3.99 ng/ml, performed in 56 (77.8%), and 12 tumors detected (detection rate 21.4%). All cancers in the study were clinically localized. Only 4 out of 15 cancers with PSA in the range 1.0-2.99 ng/ml (26.7%) fulfilled clinical criteria of insignificant cancer. Two were poorly differentiated and found to have patologically extracapsular disease. None of the 12 patients with PCa and PSA between 3.0 and 3.99 ng/ml had poorly differentiated features and only one complied with criteria of insignificant cancer. One out of seven who underwent RRP was found to have extracapsular disease. CONCLUSIONS: Cancer detection in low PSA ranges is lower but still relevant. The detection of potentially aggresive cancers is still of concern.

PSA-use in a Spanish industrial area.

OBJECTIVES: To document the extent of prostate-specific antigen (PSA)-testing in the general population at Getafe (Spain) outside our prostate cancer (PC) screening program, and to check its performance in terms of PC detection. METHODS: A total of 5371 PSA-test records (1997-1999) were reviewed and testing rates estimated per 1000 person-years. The extent of patient referral (men referred to our facilities) was calculated adjusting for PSA levels. To approach the performance of testing in the general population, our PC screening program acted as a standard for comparison. The probability of missing one PC in the general population was estimated in terms of number of men necessary to screen (NNS). Calculations were made adjusting for PSA levels. RESULTS: PSA-testing rate in the general population was 21.6/1000 person-years. In the age-group 55-69 years, this rate was 86.8/1000 (152.6 in men >70 years). Referral rates were 67.9 and 39.5% for men with PSA 4-10 and >10 ng/ml, respectively. Overall PC detection rate was 1.76%. Detection rates for PSA 4-10 and >10 ng/ml were 4.66 and 12.94%, respectively. When compared with the performance of the screening program, for every 17 men with a PSA in the range 4-10 ng/ml one cancer was missed (95% confidence interval (CI), 9-580). Similarly, one cancer was lost for every four men with a PSA >10 ng/ml (95% CI, 2-8). CONCLUSIONS: The extent of opportunistic testing in our setting is very high, particularly in the older age groups. Opportunistic screening renders PC detection rates lower than expected for every PSA level and cannot be encouraged.