What is the efficacy of screening in reducing all-cause mortality or hospital admission?

Efficacy of Screening in Reducing All-Cause Mortality or Hospital Admission

Screening programs show variable effectiveness in reducing all-cause mortality, with only a few specific screening interventions demonstrating modest reductions in all-cause mortality, while most show benefits limited to disease-specific mortality.

Evidence for All-Cause Mortality Reduction

Lung Cancer Screening

• Low-dose computed tomography (LDCT) screening for lung cancer in high-risk individuals demonstrates a 6.7% reduction in all-cause mortality (RR 0.93; 95% CI, 0.86-0.99) according to the National Lung Screening Trial (NLST) 1
• The majority of this all-cause mortality reduction is attributable to fewer deaths from lung cancer specifically 1
• The number needed to screen with LDCT to save one life over 6.5 years of follow-up is 320 1
• Smaller trials like DANTE and DLCST have not observed significant differences in all-cause mortality rates 1

Colorectal Cancer Screening

• Biennial fecal occult blood test (FOBT) screening shows a small but statistically significant 2% reduction in all-cause mortality among compliant participants over 30 years of follow-up (RR 0.98; 95% CI, 0.97-0.99) 2
• The reduction in colorectal cancer mortality was greater for men (RR 0.75; 95% CI, 0.62-0.90) than women (RR 0.91; 95% CI, 0.75-1.09) 2

Breast Cancer Screening

• Despite demonstrated reductions in breast cancer-specific mortality with mammography screening, all-cause mortality reduction has not been conclusively demonstrated 3, 4
• The size of a randomized trial required to demonstrate a reduction in all-cause mortality for breast cancer screening would need to be at least 10 times larger than trials powered to test for disease-specific mortality reduction 4

Evidence for Disease-Specific Mortality Reduction

Prostate Cancer Screening

• The European Randomized Study of Screening for Prostate Cancer (ERSPC) showed a 20% reduction in prostate cancer mortality after 13 years (RR 0.79; 95% CI, 0.69-0.91) 1
• The Göteborg randomized trial showed a 44% reduction in prostate cancer mortality after 14 years (rate ratio 0.56; 95% CI, 0.39-0.82) 1
• However, PSA screening has not demonstrated a reduction in all-cause mortality 1
• The USPSTF found insufficient evidence to determine the net benefit of prostate cancer screening in men younger than 75 years 1

Skin Cancer Screening

• No evidence shows that skin cancer screening reduces all-cause mortality 1
• A German national skin cancer screening program showed no observable melanoma mortality benefit compared to other European countries 1
• A nonrandomized study from the German screening program initially showed lower melanoma mortality in the screened group, but this difference was attenuated after adjustment for lead time bias 1

Breast Cancer Screening

• Mammography screening demonstrates a 22-40% reduction in breast cancer-specific mortality 3
• The Swedish Two-County trial showed a 27-31% reduction in breast cancer mortality after 29 years of follow-up 3
• Annual screening mammography for women 40-84 years decreases breast cancer mortality by 40% (12 lives per 1,000 women screened) 3

Systematic Review Findings

• A systematic review of meta-analyses and randomized trials found that among currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon 5
• Reductions in all-cause mortality are very rare or non-existent in most screening programs 5
• Among individual randomized controlled trials, reductions in disease-specific mortality where the 95% confidence intervals excluded the null occurred in only 30% of estimates 5
• For all-cause mortality, significant reductions occurred in only 11% of estimates 5

Factors Affecting Screening Effectiveness

Participation Rates

• Effective interventions to increase participation in screening programs include postal reminders (breast RR=1.37; cervical RR=1.71; colorectal RR=1.33) and telephone reminders 6
• GP's signature on invitation letters increases participation (breast RR=1.13; cervical RR=1.20; colorectal RR=1.15) 6
• Scheduled appointments instead of open appointments improve participation (breast RR=1.26; cervical RR=1.49; colorectal RR=1.79) 6

Biomarker Limitations

• Among biomarkers evaluated as screening tests, only fecal occult blood testing in colorectal cancer screening has unequivocally been shown to reduce mortality 7
• Lack of sensitivity and specificity, combined with low prevalence of specific cancers in asymptomatic populations, limit the effectiveness of many biomarker-based screening approaches 7

Clinical Implications

• When considering implementation of screening programs, focus should be placed on interventions with demonstrated mortality benefits 5
• The balance between benefits and harms must be carefully evaluated, as many screening programs fail to demonstrate all-cause mortality reduction despite disease-specific benefits 4, 5
• Lung cancer screening with LDCT in high-risk individuals currently shows the strongest evidence for all-cause mortality reduction 1