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.)

Background The European Randomized study of Screening for Prostate Cancer (ERSPC) is a randomized multi-center trial with a predefined centralized database, analysis plan and core age group (55–69 years) evaluating prostate-specific antigen (PSA) testing in eight European countries. Methods The present results are based on prostate cancer (PCa) incidence and mortality truncated at 9, 11, and 13 years of follow-up in the intervention arm (offered PSA testing) relative to the control arm. A secondary analysis corrected for selection bias due to non-participation was performed. Because of incomplete follow-up, only incidence and no mortality data at 9 years follow-up are reported for the French centers. Findings The rate ratio (RR) of PCa incidence between the intervention and control arms was 1.91 after 9 years (1.64 including France), 1.66 after 11 years and 1.57 after 13 years. The RR of PCa mortality was 0.85, 0.78 and 0.79 at 9, 11 and 13 years respectively (95% confidence interval 13-year 0.69–0.91, p = 0.001). This corresponds to a relative risk reduction of 21% and an absolute risk reduction of death from PCa at 13 years of 0.11 per 1,000 person-years or 1.28 per 1,000 men randomized, which is equivalent to one PCa death averted per 781 men invited for screening or one per 27 additional PCa detected. PCa mortality reduction in screened men after adjustment for non–participation was 27%. Interpretation This update of ERSPC confirms a substantial PCa mortality reduction due to PSA testing, with a substantially increased absolute effect at 13 years compared to findings after 9 and 11 years. Funding All sources of funding per center are indicated in the “Web extra material” section. Trial identification This trial is registered under Current Controlled Trials number: ISRCTN49127736.

Summary Background Several trials have evaluated the effect of prostate-specific antigen (PSA)-based screening on prostate cancer (PC) mortality, with conflicting results. We report on the mortality in the European Randomized Trial of Screening for Prostate Cancer (ERSPC) with two added years of follow-up. Methods The ERSPC is a randomized screening trial in men aged 50 – 74 years (N=182,160) at entry, with a predefined core age group of 55 – 69 years (N=162,388) conducted in eight European countries Men randomized to the intervention arm were offered prostate specific antigen (PSA)-based screening while those in the control arm were not offered screening. The primary outcome is PC mortality. Results After a median follow-up of 11 years the relative risk reduction for PC death in the intention to screen analysis was 21% (risk ratio 0.79, 95%CI 0.68 – 0.91, p=0.001), and 29% for screened men after correction for non-compliance in the core age group. The absolute difference in mortality amounted to 0.10 per 1000 person years or 1.07 per 1000 men randomized. The rate ratio of PC mortality during the follow-up years 10 -11 was 0.62 (95% CI 0.45 – 0.85, P=0.003). The numbers needed invite (NNI) and detect (NND) to prevent one PC death amounted to 1055 and 37 at 11 years of follow-up and 936 and 33 for the entire follow-up. There was no difference in all-cause mortality. Conclusions Two added years of follow-up consolidate our previous finding that PSA-based screening reduces PC mortality but does not affect all cause mortality. (The trial is registered in the ISRCTN registry under number 49127736.)

No abstract

No abstract

Summary Background Prostate cancer is one of the leading causes of death from malignant disease among men in the Western world. One strategy to decrease the risk of dying from this disease is screening with Prostate-Specific Antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. Methods In December 1994, 20 000 men born 1930 to 1944, randomly sampled from the Population Register, were computer randomised in a 1:1 ratio to a screening group invited for biennial PSA testing or to a control group not invited. In each arm, 48 men were excluded from analysis due to either death or emigration before randomization date or prevalent prostate cancer. The primary endpoint was prostate cancer specific mortality analyzed according to the intention-to-screen principle. Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with elevated PSA were offered additional tests such as digital rectal examination and prostate biopsies. The study is still ongoing inviting men who have not yet reached the upper age limit. This is the first planned report on cumulative prostate cancer incidence and mortality calculated up to Dec 31 2008. This study is registered [as an International Standard Randomised Controlled Trial], number [ISRCTN49127736]. Findings Among men randomised to screening 7578/9952 (76%) attended at least once (attendees). During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer resulting in a cumulative incidence of prostate cancer of 12.7% in the screening arm and 8.2% in the control arm (hazard ratio 1.64; 95% confidence interval [CI] 1.50–1.80; p<0.0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40% (95% CI 0.17–0.64%), from 0.90% in the control group to 0.50% in the screening group. The incidence rate ratio for death from prostate cancer was 0.56 (95% CI 0.39–0.82; p=0.002) in the screening compared to the control group. The incidence rate ratio of attendees compared to the control group was 0.44 (95% CI 0.28–0.68; p=0.0002). Overall, 293 men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. Interpretation The benefit of prostate cancer screening compares favourably to other cancer screening programs and in this study prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over diagnosis is substantial and the number needed to treat is at least as high as in breast cancer screening. Funding The Swedish Cancer Society, the Swedish Research Council and the National Cancer Institute.

A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

In developed countries, prostate cancer is the second most frequently diagnosed cancer, and the third most common cause of death from cancer in men. Apart from age and ethnic origin, a positive family history is probably the strongest known risk factor. Clinically, prostate cancer is diagnosed as local or advanced, and treatments range from surveillance to radical local treatment or androgen-deprivation treatment. Androgen deprivation reduces symptoms in about 70-80% of patients with advanced prostate cancer, but most tumours relapse within 2 years to an incurable androgen-independent state. The recorded incidence of prostate cancer has substantially increased in the past two decades, probably because of the introduction of screening with prostate-specific antigen, the use of improved biopsy techniques for diagnosis, and increased public awareness. Trends in mortality from the disease are less clearcut. Mortality changes are not of the same magnitude as the changes in incidence, and in some countries mortality has been stable or even decreased. The disparity between reported incidence and mortality rates leads to the probable conclusion that only a small proportion of diagnosed low-risk prostate cancers will progress to life-threatening disease during the lifetime of the patient.