Prostate-Cancer Mortality at 11 Years of Follow-up

Abstract

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.)

PSA screening for prostate cancer: why so much controversy?

“…We then decided to start in 1988 the first randomized and prospective trial of screening for prostate cancer with the hope of being able to diagnose the disease at the localized, asymptomatic and only potentially curable stage. 10,11 Results of prospective and randomized screening studies An update at 11 years of follow-up of the ERSPC which started in 1991 with last enrolment in 2003 (162 388 men aged 55-69 years of age) shows a 21% reduction (95% confidence interval (CI): 0.68-0.91) in the rate of prostate cancer deaths with 299 deaths from prostate cancer in the screened group and 462 in the control group 12 (Table 1). During years 10 and 11 of follow-up, the relative risk reduction was 38% (95% CI: 0.45-0.85, P50.003), an observation expected from the long time survival of men diagnosed with early prostate cancer.…”

“…It is important to mention that the majority of deaths which occurred in the screen-detected cancers in both the ERSPC and Quebec studies were cancers detected at first screening, namely, 74% 12 and 73%, 14 respectively (Table 1). It seems reasonable to believe that if these men had been previously screened in the course of an appropriate screening schedule, most of them would have been diagnosed at a localized stage.…”

“…Since 45% and 52% of men had screening before and during the trial, respectively, in the 'control/usual care' arm, the PLCO trial is not a trial evaluating the effect of screening on prostate cancer death since, as mentioned above, 19 only 12% more men had screening in the intervention arm. This was also clearly stated by: 12 'the study ultimately became one that compared organized screening with non organized screening and therefore does not contribute to the evaluation of the effect of population-based screening'.…”

Updated results from the European Randomized Study of Prostate-Specific Antigen (PSA) Screening for Prostate Cancer: are Asian countries encouraged to promote PSA screening?

“…Furthermore, a recent article that reports on 2 additional years of observation in the ERSPC study has confirmed a positive effect of PSA screening by noting that screening reduced the PCa death rate (21% reduction). 3 After adjustments for non-compliance and selection bias, the risk reduction rate reached 29%. Despite these results, the USPSTF maintains their recommendation grade as 'D', which means that there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.…”

Prostate Cancer Screening: A Complicated Puzzle, Explanation Needed

“…But two landmark studies in the past year, involving over 200,000 men, provide clear evidence that if there is a benefit from prostate cancer screening, it is small, and it may be outweighed by the potential harms brought about by screening. 1,2 It wasn't supposed to be this way. Once all the data was in, we were supposed to have a clearer idea whether this was a good test or not.…”