Prostate Cancer Mortality in the Finnish Randomized Screening Trial

Finnish Cancer Registry, Helsinki, Finland (NM, MH, LM)
Journal of the National Cancer Institute (Impact Factor: 12.58). 03/2013; 105(10). DOI: 10.1093/jnci/djt038
Source: PubMed


Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality.MethodsA total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0ng/mL or 3.0 to 3.99ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided.ResultsPC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). No statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms.Conclusions
At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.

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    • "Results from a single ERSPC center are insufficient for conclusive evidence on screening. Detailed analyses comparing outcomes of ERSPC [3] [4] and comparing these with outcomes of the US Prostate, Lung, Colorectal, and Ovary (PLCO) cancer screening trial [14] are ongoing and might relate to the differences in background incidence, contamination rate, screening interval, and percentage of men biopsied. "
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    ABSTRACT: BACKGROUND: Evidence from randomized trials on the effects of screening for prostate cancer (PCa) on disease-specific mortality accumulates slowly with increasing follow-up. OBJECTIVE: To assess data on PCa-specific mortality in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial with randomization after signed, written informed consent (efficacy trial). In the period 1993-1999, a total of 42 376 men aged 54-74 yr were randomized to a screening arm (S-arm) (n = 21 210 with screening every 4 yr, applying a total prostate-specific antigen [PSA] level cut-off ≥3.0 ng/ml as biopsy indication) or a control arm (C-arm) (n = 21 166; no intervention). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Number of PCas detected per arm depicted by predefined time periods and prognostic groups. PCa-specific mortality analyses using Poisson regression in age group 55-74 yr at randomization and separately in the predefined age group of 55-69 yr. RESULTS AND LIMITATIONS: After a median follow-up of 12.8 yr, 19 765 men (94.2%) were screened at least once and 2674 PCas were detected (of which 561 [21.0%] were interval PCas). In the C-arm, 1430 PCas were detected, resulting in an excess incidence of 59 PCas per 1000 men randomized (61 PCas per 1000 in age group 55-69 yr). Thirty-two percent of all men randomized have died. PCa-specific mortality relative-risk (RR) reductions of 20.0% overall (age: 55-74 yr; p = 0.042) and 31.6% (age: 55-69 yr; p = 0.004) were found. A 14.1% increase was found in men aged 70-74 yr (not statistically significant). Absolute PCa mortality was 1.8 per 1000 men randomized (2.6 per 1000 men randomized in age group 55-69 yr). The number needed to invite and number needed to manage were 565 and 33, respectively, for age group 55-74 yr, and 392 and 24, respectively, for age group 65-69 yr. Given the slow natural history of the disease, follow-up might be too short. CONCLUSIONS: Systematic PSA-based screening reduced PCa-specific mortality by 32% in the age range of 55-69 yr. The roughly twofold higher incidence in the S-arm underlines the importance of tools to better identify those men who would benefit from screening.
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    ABSTRACT: In the healthcare political discussions on treatment measures, the controversy over prostate-specific antigen (PSA) screening has taken a leading role in comparison to, for example the relatively undisputed role of breast and colon screening. This has fortunately led to an in-depth critical analysis of the available data. One advantage is the benefit on survival which increases with longer follow-up observation times. When carrying out studies the quantitative extent of this benefit can become obscured by prescreening, prevalent screening, lack of compliance, contamination and healthy screen bias. Nevertheless, the European randomized screening study of prostate cancer (ERSPC) study, for example, showed sufficient statistical power to confirm a screening benefit after 9 or 11 years (evidence level A). However, even for prostate cancer the internal problems of preventive medicine of overdiagnosis and overtherapy are also partially dependent on the age range of the screening population and the screening frequency (28-52 %). Unnecessary deficits in the quality of life reduce the benefit of survival in these patients. By using a PSA fine tuning and risk stratification, approximately one third of diagnoses and therapies can be avoided. Additionally, the active surveillance of tumors unsuitable for treatment together with an improved quality of therapy should become of greater importance.
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