Search

Importance: Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment., Objective: To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality., Design, Setting, and Participants: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016., Intervention: An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice., Main Outcomes and Measures: Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic., Results: Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66)., Conclusions and Relevance: Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening., Trial Registration: ISRCTN Identifier: ISRCTN92187251.

Background: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes., Methods: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015)., Results: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis., Conclusions: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials.

Background: In cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers' ability to correctly guess the trial arm., Methods: Over 550 General Practitioner (GP) practices (>415,000 men aged 50-69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm., Results: 1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation., Conclusions: It is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them., Trial Registration: ISRCTN92187251.

OBJECTIVE • To estimate rates of prostate-specific antigen (PSA) testing in UK general practices by age, deprivation index and geographical location. SUBJECTS AND METHODS • Practice-based, retrospective data on PSA testing patterns in 2007 were collected from a random sample of 87 general practices using EMIS LV computer systems within the passively observed non-intervention arm of a cluster-randomized controlled trial. • Information for a total of 126 716 men aged 45-89 years with no recorded diagnosis of prostate cancer prior to 1 January 2007 was collected. RESULTS • In all, 7902 (6.2%) of 126 716 men aged 45-89 without a prior diagnosis of prostate cancer underwent at least one PSA test from their general practitioner during 2007 [95% confidence interval (CI) 5.6-7.0%; practice-based inter-quartile range 3.6-8.4%]. • PSA testing rates were 1.4% (95% CI 1.1-1.6%) in men aged 45-49, rising to 11.3% (95% CI 10.0-12.9%) at age 75-79 years (P for trend <0.001). • Testing rates were lowest in the three northern centres (3.5-5.7%) vs the three more southern centres (7.1-8.9%; P < 0.001). • For every 20 points increase in the index of multiple deprivation score, the proportion of men tested fell by 1.7% (95% CI -2.5 to -0.8%; P < 0.001). • Lower proportions of men were subsequently diagnosed with prostate cancer in practices testing more men (odds ratio for a one unit increase in the natural log of testing 0.76; 95% CI 0.60-0.97; P= 0.025). CONCLUSION • Overall levels of PSA testing in UK general practice remain low, but for those tested there are important variations by age, deprivation and geographical location that do not appear to reflect clinical need or the intention of current policy. • PSA testing in general practice is currently skewed towards older men, and current policy enabling all men to make an informed choice about PSA testing is not being effectively implemented as uptake clearly varies by socioeconomic status. • This reinforces the need for robust evidence regarding the costs and benefits of using the PSA test for the detection of localized prostate cancer in the UK, a full assessment of the health economic implications and a revision of the current policy., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)