Screening for prostate cancer.
ABSTRACT Any form of screening aims to reduce disease-specific and overall mortality, and to improve a person's future quality of life. Screening for prostate cancer has generated considerable debate within the medical and broader community, as demonstrated by the varying recommendations made by medical organizations and governed by national policies. To better inform individual patient decision-making and health policy decisions, we need to consider the entire body of data from randomised controlled trials (RCTs) on prostate cancer screening summarised in a systematic review. In 2006, our Cochrane review identified insufficient evidence to either support or refute the use of routine mass, selective, or opportunistic screening for prostate cancer. An update of the review in 2010 included three additional trials. Meta-analysis of the five studies included in the 2010 review concluded that screening did not significantly reduce prostate cancer-specific mortality. In the past two years, several updates to studies included in the 2010 review have been published thereby providing the rationale for this update of the 2010 systematic review.
To determine whether screening for prostate cancer reduces prostate cancer-specific mortality or all-cause mortality and to assess its impact on quality of life and adverse events.
An updated search of electronic databases (PROSTATE register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CANCERLIT, and the NHS EED) was performed, in addition to handsearching of specific journals and bibliographies, in an effort to identify both published and unpublished trials.
All RCTs of screening versus no screening for prostate cancer were eligible for inclusion in this review.
The original search (2006) identified 99 potentially relevant articles that were selected for full-text review. From these citations, two RCTs were identified as meeting the inclusion criteria. The search for the 2010 version of the review identified a further 106 potentially relevant articles, from which three new RCTs were included in the review. A total of 31 articles were retrieved for full-text examination based on the updated search in 2012. Updated data on three studies were included in this review. Data from the trials were independently extracted by two authors.
Five RCTs with a total of 341,342 participants were included in this review. All involved prostate-specific antigen (PSA) testing, with or without digital rectal examination (DRE), though the interval and threshold for further evaluation varied across trials. The age of participants ranged from 45 to 80 years and duration of follow-up from 7 to 20 years. Our meta-analysis of the five included studies indicated no statistically significant difference in prostate cancer-specific mortality between men randomised to the screening and control groups (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.86 to 1.17). The methodological quality of three of the studies was assessed as posing a high risk of bias. The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were assessed as posing a low risk of bias, but provided contradicting results. The ERSPC study reported a significant reduction in prostate cancer-specific mortality (RR 0.84, 95% CI 0.73 to 0.95), whilst the PLCO study concluded no significant benefit (RR 1.15, 95% CI 0.86 to 1.54). The ERSPC was the only study of the five included in this review that reported a significant reduction in prostate cancer-specific mortality, in a pre-specified subgroup of men aged 55 to 69 years of age. Sensitivity analysis for overall risk of bias indicated no significant difference in prostate cancer-specific mortality when referring to the meta analysis of only the ERSPC and PLCO trial data (RR 0.96, 95% CI 0.70 to 1.30). Subgroup analyses indicated that prostate cancer-specific mortality was not affected by the age at which participants were screened. Meta-analysis of four studies investigating all-cause mortality did not determine any significant differences between men randomised to screening or control (RR 1.00, 95% CI 0.96 to 1.03). A diagnosis of prostate cancer was significantly greater in men randomised to screening compared to those randomised to control (RR 1.30, 95% CI 1.02 to 1.65). Localised prostate cancer was more commonly diagnosed in men randomised to screening (RR 1.79, 95% CI 1.19 to 2.70), whilst the proportion of men diagnosed with advanced prostate cancer was significantly lower in the screening group compared to the men serving as controls (RR 0.80, 95% CI 0.73 to 0.87). Screening resulted in a range of harms that can be considered minor to major in severity and duration. Common minor harms from screening include bleeding, bruising and short-term anxiety. Common major harms include overdiagnosis and overtreatment, including infection, blood loss requiring transfusion, pneumonia, erectile dysfunction, and incontinence. Harms of screening included false-positive results for the PSA test and overdiagnosis (up to 50% in the ERSPC study). Adverse events associated with transrectal ultrasound (TRUS)-guided biopsies included infection, bleeding and pain. No deaths were attributed to any biopsy procedure. None of the studies provided detailed assessment of the effect of screening on quality of life or provided a comprehensive assessment of resource utilization associated with screening (although preliminary analyses were reported).
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.
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ABSTRACT: The paper describes the use of frequentist and Bayesian shared-parameter joint models of longitudinal measurements of prostate-specific antigen (PSA) and the risk of prostate cancer (PCa). The motivating dataset corresponds to the screening arm of the Spanish branch of the European Randomized Screening for Prostate Cancer study. The results show that PSA is highly associated with the risk of being diagnosed with PCa and that there is an age-varying effect of PSA on PCa risk. Both the frequentist and Bayesian paradigms produced very close parameter estimates and subsequent 95% confidence and credibility intervals. Dynamic estimations of disease-free probabilities obtained using Bayesian inference highlight the potential of joint models to guide personalized risk-based screening strategies.Journal of Applied Statistics 02/2015; 42(6). DOI:10.1080/02664763.2014.999032 · 0.45 Impact Factor
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ABSTRACT: Several popular screening tests, such as mammography and prostate-specific antigen, have met with wide controversy and/or have lost their endorsement recently. We systematically evaluated evidence from randomized controlled trials (RCTs) as to whether screening decreases mortality from diseases where death is a common outcome. We searched three sources: United States Preventive Services Task Force (USPSTF), Cochrane Database of Systematic Reviews, and PubMed. We extracted recommendation status, category of evidence and RCT availability on mortality for screening tests for diseases on asymptomatic adults (excluding pregnant women and children) from USPSTF. We identified meta-analyses and individual RCTs on screening and mortality from Cochrane and PubMed. We selected 19 diseases (39 tests) out of 50 diseases/disorders for which USPSTF provides screening evaluation. Screening is recommended for 6 diseases (12 tests) out of the 19. We assessed 9 non-overlapping meta-analyses and 48 individual trials for these 19 diseases. Among the results of the meta-analyses, reductions where the 95% confidence intervals (CIs) excluded the null occurred for four disease-specific mortality estimates (ultrasound for abdominal aortic aneurysm in men; mammography for breast cancer; fecal occult blood test and flexible sigmoidoscopy for colorectal cancer) and for none of the all-cause mortality estimates. Among individual RCTs, reductions in disease-specific and all-cause mortality where the 95% CIs excluded the null occurred in 30% and 11% of the estimates, respectively. Among currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and reductions in all-cause mortality are very rare or non-existent. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.International Journal of Epidemiology 01/2015; DOI:10.1093/ije/dyu140 · 9.20 Impact Factor
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ABSTRACT: Prostate cancer is a common malignancy in the United States that results in over 30,000 deaths per year. The current state of prostate cancer diagnosis, based on PSA screening and sextant biopsy, has been criticized for both overdiagnosis of low-grade tumors and underdiagnosis of clinically significant prostate cancers (Gleason score ≥7). Recently, image guidance has been added to perform targeted biopsies of lesions detected on multi-parametric magnetic resonance imaging (mpMRI) scans. These methods have improved the ability to detect clinically significant cancer, while reducing the diagnosis of low-grade tumors. Several approaches have been explored to improve the accuracy of image-guided targeted prostate biopsy, including in-bore MRI-guided, cognitive fusion, and MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent advances in these image-guided targeted prostate biopsy techniques.Abdominal Imaging 01/2015; DOI:10.1007/s00261-015-0353-8 · 1.91 Impact Factor