What screening interventions improve all-cause mortality?

Screening Interventions That Reduce All-Cause Mortality

Low-dose computed tomography (LDCT) lung cancer screening in high-risk individuals is the only screening intervention with robust evidence for reducing all-cause mortality, demonstrating a 6.7% reduction (RR 0.93; 95% CI 0.86-0.99) with a number needed to screen of 320 over 6.5 years. 1

Lung Cancer Screening: The Clear Winner

LDCT screening for lung cancer stands alone as the screening intervention with proven all-cause mortality benefit. The evidence is compelling:

• Target population: Adults aged 55-80 years with ≥30 pack-year smoking history who currently smoke or quit within the past 15 years 2
• Mortality reduction: The National Lung Screening Trial demonstrated both a 20% reduction in lung cancer-specific mortality AND a 6.7% reduction in all-cause mortality 2, 1
• European validation: The NELSON trial confirmed these findings with a 24% reduction in lung cancer mortality among men and 33% among women, plus a 3% relative reduction in all-cause mortality across pooled trials 2
• Cost-effectiveness: LDCT screening costs approximately €14,000-€17,000 per quality-adjusted life year gained, well below most willingness-to-pay thresholds 2

The key distinction: While other screening programs reduce disease-specific mortality, only LDCT lung cancer screening has demonstrated a statistically significant reduction in deaths from all causes. 1

Screening Interventions That Do NOT Reduce All-Cause Mortality

Colorectal Cancer Screening

Despite reducing colorectal cancer-specific mortality, screening with guaiac fecal occult blood testing (gFOBT) showed no reduction in all-cause mortality in any trial or pooled results (RR 0.82 for CRC mortality but no effect on overall survival). 2 The absolute benefit varies dramatically by age: number needed to screen is 2,655 for ages 45-59 versus 492 for ages 60-80. 2

Prostate Cancer Screening

PSA screening emphatically does not reduce all-cause mortality:

• European ERSPC trial: Identical all-cause mortality in screened versus control groups (RR 1.00,95% CI 0.98-1.02) after 11 years 3
• U.S. PLCO trial: No reduction in all-cause mortality through 13 years 3
• Why it fails: Only 2.7% of deaths in the screening age group are due to prostate cancer; competing mortality from cardiovascular disease and other causes dominates 3
• Treatment harms offset any benefit: Up to 5 per 1,000 men die within 1 month of prostate cancer surgery, and 200-300 per 1,000 experience permanent urinary incontinence or erectile dysfunction 3

Breast Cancer Screening

Mammography reduces breast cancer-specific mortality by 22-40% but has not been shown to reduce all-cause mortality in randomized trials. 4 The mortality benefit is disease-specific only:

• Women aged 40-49: 48% reduction in breast cancer mortality among those screened 4
• Women aged 50-69: 44% reduction in breast cancer mortality 4
• Annual screening saves approximately 12 lives per 1,000 women screened, but this represents breast cancer deaths only 4

General Health Checks

Comprehensive health checks for multiple diseases showed no effect on all-cause mortality (RR 0.99,95% CI 0.95-1.03) across 9 trials with 155,899 participants and median 9-year follow-up. 5 These checks also failed to reduce cardiovascular mortality (RR 1.03) or cancer mortality (RR 1.01). 5

Diabetes and Prediabetes Screening

Two randomized trials of diabetes screening (25,120 participants) found no significant difference in all-cause or cause-specific mortality at 10 years between screening and control groups. 6

Hypertension Screening

Despite hypertension being a major risk factor for cardiovascular disease, no studies have evaluated whether screening strategies for hypertension reduce morbidity or mortality—the assumption remains untested in rigorous research. 7

Critical Clinical Algorithm

For patients asking about screening to live longer:

1. Age 55-80 with significant smoking history (≥30 pack-years, current or quit ≤15 years ago): Recommend annual LDCT lung cancer screening—this is the only screening proven to reduce all-cause mortality 2, 1

2. For all other screening decisions: Counsel patients that while disease-specific screening (colorectal, breast, cervical) reduces deaths from those specific cancers, none have been proven to extend overall lifespan 2, 4, 5

3. Avoid PSA screening for mortality reduction: Explicitly state that PSA screening does not reduce all-cause mortality and carries substantial treatment-related harms 3

4. Focus prevention efforts on interventions proven to reduce all-cause mortality: Blood pressure control, statins when appropriate, and multifactorial lifestyle interventions have stronger evidence for reducing overall mortality than most screening programs 8

Common Pitfalls to Avoid

• Do not conflate disease-specific mortality with all-cause mortality: A screening test may reduce cancer deaths while having no impact on how long patients actually live 3, 5
• Recognize competing mortality: In older adults, most deaths result from cardiovascular disease, not the cancers being screened for 3
• Account for lead-time bias: Earlier diagnosis does not necessarily mean longer life, just longer awareness of disease 5
• Consider treatment harms: Screening leads to interventions that carry their own mortality risks, potentially offsetting any benefit 3, 6