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ERSPC 13-Year Follow-up: Reduction in Prostate Cancer Mortality With PSA Screening, but High Overdiagnosis Rates Remain a Concern, Say Authors

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Key Points

  • Screening was associated with a 21% reduction in risk for prostate cancer mortality and a 27% reduction after adjustment for nonparticipation.
  • The number needed to invite (NNI) of 781 and number needed to detect (NND) of 27 to prevent one prostate cancer death represent a greater absolute benefit of screening than the NNI of 1,410 and NND of 48 after 9 years of follow-up and the NNI of 979 and NND of 35 at 11 years.

The 13-year follow-up of the European Randomized Study of Screening for Prostate Cancer (ERSPC), reported by Schröder et al in The Lancet, showed that prostate-specific antigen (PSA) screening in men aged 55 to 69 years is associated with a 21% reduction in risk of prostate cancer mortality and with an increase in absolute benefit since the 9- and 11-year follow-ups. However, given the potential harms associated with overdiagnosis in screening (estimated by the authors to include 40% to 50% of screen-detected cases) and resultant overtreatment, the authors concluded that population-based screening could not yet be recommended.  

Study Details

In the ERSPC, men aged 50 to 74 years identified from population registries in eight European countries (the Netherlands, Belgium, Sweden, Finland, Italy, Spain, Switzerland, and France) were randomly assigned to PSA screening or no intervention. The screening interval was 4 years (2 years in Sweden). Screening was discontinued after two rounds in France and three rounds in Belgium, Finland, and Spain, and continued for up to five rounds in the Netherlands and 10 in Sweden.

The primary endpoint of the study was prostate cancer mortality in the core age group of 55 to 69 years on an intent-to-treat basis. A secondary analysis of mortality in screened men was performed to correct for selection bias due to nonparticipation.

Data from France are included in the assessment of 9-year prostate cancer incidence but not in assessment of mortality, due to incomplete follow-up through 2010. The analysis of mortality in the core age group includes 162,388 randomized men and the analysis in the entire cohort includes 181,999 randomized men.

Incidence in Core Age Group

In the core age group (excluding France), 7,408 prostate cancer cases were diagnosed in the screening group and 6,107 were diagnosed in the control group. The rate ratio of prostate cancer incidence for the screening vs control groups was 1.91 (95% confidence interval [CI] = 1.83–1.99) after 9 years (1.64, 95% CI = 1.58–1.69, including France), 1.66 (95% CI = 1.60–1.73) after 11 years, and 1.57 (95% CI = 1.51–1.62) after 13 years.

Risk Reduction

The rate ratio of prostate cancer mortality for the core intervention vs control groups was 0.85 (95% CI = 0.70–1.03) after 9 years, 0.78 (95% CI = 0.66–0.91) after 11 years, and 0.79 (95% CI = 0.69–0.91, P = .001) after 13 years.

The absolute risk reduction at 13 years (after adjustment for a randomization ratio of 1:1.5 in Finland) was 0.11 per 1,000 person-years or 1.28 per 1,000 men randomized, which is equivalent to 1 prostate cancer death prevented per 781 (95% CI = 490–1929) men invited for screening (number needed to invite, NNI) or 1 per 27 (95% CI = 17-66) additional prostate cancers detected (number needed to detect, NND). These figures represent improvements from the NNI of 1,410 and NND of 48 (risk reduction of 0.10/1,000 person-years and 1.02/1,000 men) observed after 9 years of follow-up and the NNI of 979 and NND of 35 (risk reduction of 0.06/1,000 person-years and 0.46/1,000 men) observed after 11 years.

After adjustment for nonparticipation, the rate ratio of prostate cancer mortality in the screening vs control groups was 0.73 (95% CI = 0.61-0.88).

Additional Findings

Screening was also associated with reduced risk of prostate cancer mortality in the entire cohort of men aged 50 to 74 years (excluding France), with a rate ratio for screening vs control of 0.83 (95% CI = 0.73–0.94, P = .004).

Analysis of prostate cancer death in the core age group at individual centers showed significantly reduced risk only in Sweden (rate ratio = 0.62, 95% CI = 0.41–0.92) and the Netherlands (rate ratio = 0.67, 95% CI = 0.51–0.88). The authors noted that a more extensive analysis of effects at individual centers that includes adjustment for noncompliance is to be performed.

There was no difference between the screening and control groups in all-cause mortality in the core age group (rate/1,000 person-years = 18.6 vs 18.9, rate ratio = 1.00, P = 0.82) or in the entire cohort (rate/1,000 person-years = 19.5 vs 19.6, rate ratio = 1.00, P = 0.98).

Conclusions

The investigators concluded, “In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening.”

They added, “Our data show a significant relative reduction in prostate cancer mortality when comparing the screening group and control group of 21% and 27% in men who participated in the study. The main weakness of screening is a high rate of overdiagnosis and overtreatment. We conclude that the time for population-based screening has not arrived. In the present situation, early diagnosis cannot be refused to men who are well informed and request to be tested. Information must concentrate on the occurrence of overdiagnosis, which is also the main target of future research. Multiparametric [magnetic resonance imaging] and the developments of new markers are the hope for the future. In the meantime available instruments with multivariate risk stratification must be applied.”

Fritz H. Schröder, MD, of Erasmus University Medical Center, is the corresponding author for The Lancet article.

Each center had its own funding responsibility. Most funding was provided by national cancer research funding agencies, European funding through Framework programs, some private sponsors, and a grant from the former Beckman/Hybritech company. For full disclosures of the study authors, visit www.thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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