Prostate-cancer mortality at 11 years of follow-up. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. Screening decreases prostate cancer mortality: 11-year follow-up of the 1988 Quebec prospective randomized controlled trial. Randomised prostate cancer screening trial: 20 year follow-up. 15-year followup of a population based prostate cancer screening study. A randomized controlled trial of shared decision making for prostate cancer screening. Does evidence-based information about screening for prostate cancer enhance consumer decision-making? A randomised controlled trial. The impact of informed consent on patient interest in prostate-specific antigen screening. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial.
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.
                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.
                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.
                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 prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.
                A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
                Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P(interaction) = .81), pretrial PSA testing (P(interaction) = .52), and comorbidity (P(interaction) = .68).
                After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing. This clinical trial is aimed at evaluating the impact of prostate cancer screening on cancer-specific mortality.
                Forty-six thousand four hundred and eighty-six (46,486) men aged 45-80 years registered in the electoral roll of the Quebec city area were randomized in 1988 between screening and no screening. Screening included measurement of serum prostatic specific antigen (PSA) using 3.0 ng/ml as upper limit of normal and digital rectal examination (DRE) at first visit. At follow-up visits, serum PSA only was used.
                Seventy-four (74) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following randomization. Median follow-up of screened men was 7.93 years. A Cox proportional hazards model of the age at death from prostate cancer shows a 62% reduction (P < 0.002, Fisher's exact test) of cause-specific mortality in the screened men (P = 0.005). These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America.
                Copyright 2004 Wiley-Liss, Inc. To assess whether screening for prostate cancer reduces prostate cancer specific mortality.
                Population based randomised controlled trial.
                Department of Urology, Norrköping, and the South-East Region Prostate Cancer Register.
                All men aged 50-69 in the city of Norrköping, Sweden, identified in 1987 in the National Population Register (n = 9026).
                From the study population, 1494 men were randomly allocated to be screened by including every sixth man from a list of dates of birth. These men were invited to be screened every third year from 1987 to 1996. On the first two occasions screening was done by digital rectal examination only. From 1993, this was combined with prostate specific antigen testing, with 4 µg/L as cut off. On the fourth occasion (1996), only men aged 69 or under at the time of the investigation were invited.
                Data on tumour stage, grade, and treatment from the South East Region Prostate Cancer Register. Prostate cancer specific mortality up to 31 December 2008.
                In the four screenings from 1987 to 1996 attendance was 1161/1492 (78%), 957/1363 (70%), 895/1210 (74%), and 446/606 (74%), respectively. There were 85 cases (5.7%) of prostate cancer diagnosed in the screened group and 292 (3.9%) in the control group. The risk ratio for death from prostate cancer in the screening group was 1.16 (95% confidence interval 0.78 to 1.73). In a Cox proportional hazard analysis comparing prostate cancer specific survival in the control group with that in the screened group, the hazard ratio for death from prostate cancer was 1.23 (0.94 to 1.62; P = 0.13). After adjustment for age at start of the study, the hazard ratio was 1.58 (1.06 to 2.36; P = 0.024).
                After 20 years of follow-up the rate of death from prostate cancer did not differ significantly between men in the screening group and those in the control group. Trial registration Current Controlled Trials, ISRCTN06342431. We evaluated long-term survival in attendees and nonattendees of a 1-time screening for prostate cancer.
                A total of 2,400 men 55 to 70 years old in 1988 were randomly selected and invited to a screening for prostate cancer. Of the invited men 1,782 (74%) attended. Screening attendees were examined with digital rectal examination, transrectal ultrasound and prostate specific antigen analysis. When cancer was suspected, prostate biopsies were taken. A total of 65 men with prostate cancer were detected by this procedure. The entire source population comprising 27,204 men, including 618 nonattendees (26%), was followed for prostate cancer diagnosis and survival for 15 years.
                Incidence rate ratios were calculated using Poisson regression models. We found no effect of this screening procedure on the risk of death from prostate cancer and other causes of death (incidence rate ratio 1.10, 95% CI 0.83-1.46 and 0.98, 95% CI 0.92-1.05, respectively) when comparing all invited men with the source population. However, attending the screening program was associated with a significantly decreased risk of death from causes other than prostate cancer (vs source population incidence rate ratio 0.82, 95% CI 0.76-0.90). In contrast, the corresponding incidence rate ratio in nonattendees was 1.53 (95% CI 1.37-1.71).
                We found no evidence of a beneficial effect of this specific screening procedure but strong evidence of a difference in overall survival in screening attendees and nonattendees. These findings should be considered when interpreting previous and upcoming studies of the effect of screening programs. To evaluate a patient-educational approach to shared decision making for prostate cancer screening.
                Randomized controlled trial with preoffice visit assessment and 2-week follow-up.
                University-based family practice center.
                Men aged 45 through 70 years with no history of prostate cancer or treatment for prostate disease (N = 160). Two patients were unavailable for follow-up.
                Twenty-minute educational videotape on advantages and disadvantages of prostate-specific antigen (PSA) screening for prostate cancer.
                A measure of patients' core knowledge of prostate cancer developed for this study, reported preferences for PSA testing, and ratings of the videotape.
                Patients' core knowledge at baseline was poor. At 2-week follow-up, subjects undergoing videotape intervention showed a 78% improvement in the number of knowledge questions answered correctly (P = .001), and knowledge increased about mortality due to early-stage prostate cancer, PSA screening performance, treatment-related complications, and disadvantages of screening. No overall change was observed for control subjects. At follow-up, 48 (62%) of 78 intervention patients planned to have the PSA test compared with 64 (80%) of 80 control patients (18.5% absolute reduction; 95% confidence interval, 4.6%-32.4%; P = .009). Intervention subjects rated favorably the amount of information provided and the clarity, balance, and length of the videotape and would recommend the videotape to others.
                Patient education regarding the potential benefits and harms of early detection of prostate cancer can lead to more informed decision making. Incorporating the PSA videotape into the periodic health examination for asymptomatic men aged 50 years and older is recommended. Efforts to educate men about the controversy surrounding prostate cancer screening are well intended but rarely evaluated rigorously. We evaluated an evidence-based (EB) booklet for men designed to promote informed decision-making. We also determined whether men's preference for involvement in decision-making ("passive", "collaborative" or "active") modified its impact.
                Men aged 40-70 years were recruited from the practices of 13 local general practitioners (GPs) in Sydney, Australia. They completed a self-administered questionnaire before seeing their GP, who, according to pre-randomised codes, distributed either our EB booklet or conventional information. Post-test questionnaires were mailed to men three days later. Of the 248 eligible men recruited, 214 (86% response rate) returned post-test questionnaires. Knowledge of evidence and of risk of developing and dying from prostate cancer, attitudes, interest in screening for prostate-specific antigen (PSA), worry and decisional conflict were the main outcome measures.
                Compared with those receiving conventional information, men receiving the EB booklet had significantly improved knowledge (50% of items correct, 95% CI 46-53%; vs 45% correct, 95% CI 42-48%) (p = 0.048) and lower levels of decisional conflict (mean 21.6, 95% CI 20.7-22.5; vs mean 24.3, 95% CI 23.4-25.2) (p < 0.001). Interest in PSA screening was significantly reduced in both groups at post-test (p < 0.001). Men preferring a "passive" approach to decision-making gained as much from our EB booklet as those with "active" or "collaborative" preferences.
                Our findings show the benefits of providing evidence-based information to men about PSA screening. Our EB booklet facilitated informed choice, even among "passive" decision-makers. Because of the many uncertainties surrounding screening for prostate cancer, authorities recommend that patients be involved in the screening decision.
                To determine the impact of informed consent on patient interest in undergoing prostate-specific antigen (PSA) screening.
                Men 50 years or older with no prior PSA testing and no history of prostate cancer presenting to 1 of 4 university-affiliated primary care practices were eligible for enrollment. Patients were randomized to receive either a scripted informational intervention simulating an informed consent presentation (intervention group, n = 103) or a single sentence about the PSA (control group, n = 102). The main outcome measure was patient interest in undergoing PSA screening measured on a 5-point Likert scale.
                Patients who received the informational intervention were significantly less interested in undergoing PSA screening than controls (mean difference in interest, 0.8 on 5-point scale, P < .001). Informed patients were much less likely to indicate high interest in screening (odds ratio, 0.34; 95% confidence interval, 0.19-0.60; P < .001). In a multivariate model, family history of prostate cancer was associated with increased interest and advancing age with decreased interest in PSA screening, but the informational intervention remained the strongest predictor of interest.
                Among primary care patients of predominantly lower socioeconomic status, those who received informed consent were significantly less interested in PSA screening than those who did not. For physicians who offer the PSA as a screening test, this finding highlights the importance of apprising patients of the associated benefits, burdens, and uncertainties and allowing them to participate in the screening decision. Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown.
                To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer.
                Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy.
                Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211).
                Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications.
                Among the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse-free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%).
                In men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00394511.
Prostate cancer screening did not significantly decrease prostate cancer-specific mortality in a combined meta-analysis of five RCTs. Only one study (ERSPC) reported a 21% significant reduction of prostate cancer-specific mortality in a pre-specified subgroup of men aged 55 to 69 years. Pooled data currently demonstrates no significant reduction in prostate cancer-specific and overall mortality. Harms associated with PSA-based screening and subsequent diagnostic evaluations are frequent, and moderate in severity. Overdiagnosis and overtreatment are common and are associated with treatment-related harms. Men should be informed of this and the demonstrated adverse effects when they are deciding whether or not to undertake screening for prostate cancer. Any reduction in prostate cancer-specific mortality may take up to 10 years to accrue; therefore, men who have a life expectancy less than 10 to 15 years should be informed that screening for prostate cancer is unlikely to be beneficial. No studies examined the independent role of screening by DRE.