Assessment of prostate-specific antigen screening: an evidence-based report by the German Institute for Quality and Efficiency in Health Care.

CONTEXT: Prostate-specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long-term disease-specific mortality, but also results in overdiagnoses and treatment-related harms. OBJECTIVE: To systematically assess the benefits and harms of population-based PSA screening and the potential net benefit to inform health policy decision-makers in Germany. EVIDENCE ACQUISITION: We performed a protocol-guided comprehensive literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. All steps were performed by one or two investigators; any discrepancies were resolved by consensus. To allow subgroup analyses for identifying the optimal screening parameters, the eight national trials conducted under the umbrella of the European Randomised study of Screening for Prostate Cancer (ERSPC) were included as individual trials. EVIDENCE SYNTHESIS: We included a total 11 randomised controlled trials (RCTs) with a total of 416 000 study participants. For all-cause mortality, we found neither benefit nor harm. PSA screening was associated with a reduced risk of both prostate cancer mortality and the development of metastases. For the outcomes of health-related quality of life, adverse effects and the consequences of false-negative screening results there was no difference; however, this was due to the lack of eligible RCT data. Finally, PSA screening was associated with large numbers of overdiagnoses with adverse downstream consequences of unnecessary treatment (e.g. incontinence, erectile dysfunction) and large numbers of false-positive PSA tests leading to biopsies associated with a small but not negligible risk of complications. Limitations of this assessment include the clinical heterogeneity and methodological limitations of the underlying studies. CONCLUSIONS: The benefits of PSA-based prostate cancer screening do not outweigh its harms. We failed to identify eligible screening studies of newer biomarkers, PSA derivatives or modern imaging modalities, which may alter the balance of benefit to harm. PATIENT SUMMARY: In the present study, we reviewed the evidence on the PSA blood test to screen men without symptoms for prostate cancer. We found that the small benefits experienced by some men do not outweigh the harms to many more men.

Screening for sickle cell disease in newborns: a systematic review.

BACKGROUND: Sickle cell disease (SCD) is an inherited autosomal recessive disorder caused by the replacement of normal haemoglobin (HbA) by mutant Hb (sickle Hb, HbS). The sickle-shaped red blood cells lead to haemolysis and vaso-occlusion. Especially in the first years of life, patients with SCD are at high risk of life-threatening complications. SCD prevalence shows large regional variations; the disease predominantly occurs in sub-Saharan Africa. We aimed to systematically assess the evidence on the benefit of newborn screening for SCD followed by an earlier treatment start. METHODS: We systematically searched bibliographic databases (MEDLINE, EMBASE, Cochrane Databases, and the Health Technology Assessment Database), trial registries, and other sources to identify systematic reviews and randomised controlled trials (RCTs) or non-randomised trials on newborn screening for SCD. The last search was in 07/2020. Two reviewers independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. Data were extracted by one person and checked by another. As meta-analyses were not possible, a qualitative summary of results was performed. RESULTS: We identified 1 eligible study with direct evidence: a Jamaican retrospective study evaluating newborn screening for SCD followed by preventive measures (prevention of infections and education of parents). The study included 500 patients with SCD (intervention group, 395; historical control group, 105). Although the results showed a high risk of bias, the difference between the intervention and the control group was very large: mortality in children decreased by a factor of about 10 in the first 5 years of life (0.02% in the intervention group vs. 0.19% in the control group, odds ratio 0.09; 95% confidence interval [0.04; 0.22], p < 0.001). CONCLUSION: The results are based on a single retrospective study including historical controls. However, the decrease of mortality by a factor of 10 is unlikely to be explained by bias alone. Therefore, in terms of mortality, data from this single retrospective study included in our systematic review suggest a benefit of newborn screening for SCD (followed by preventive measures) versus no newborn screening for SCD (weak certainty of conclusions).