The association between the impact of cancer screening on early-stage cancers and on cancer mortality: A systematic review and meta-analysis

Background Cancer-specific mortality traditionally has been used to evaluate the effectiveness of cancer screening, and reduction of late-stage disease has been found to correlate with reduction of cancer-specific mortality, but measurement requires long follow-up. Increased detection of early-stage cancer has been proposed as a potential early indicator of beneficial interventions. Our systematic review and meta-analysis evaluated trial-level correlations between early-stage outcomes (early-stage cancer incidence, proportion of screen-detected cancers, diagnostic yield of screening) and cancer-specific mortality from all available cancer screening randomised controlled trials (RCTs). Methods Weighted Pearson correlation coefficients were estimated for early-stage diagnosis outcomes (log relative risk for early-stage cancer incidence; proportion otherwise) and cancer-specific mortality. Results We included 213 publications from 58 trials (62 trial-arm comparisons) covering 10 cancer types, but only 15 trials reported cancer stage at a timepoint prior to mortality. The correlation between early-stage cancer incidence and cancer mortality was −0.25 (95% CI: −0.49 to 0.07; 43 trials). This was similar by cancer type (e.g., lung [ n = 14]: −0.36 [95% CI: −0.69 to 0.15]; breast [ n = 13]: −0.21 [95% CI: −0.61 to 0.42]). The correlation for the proportion of screen-detected cancers was −0.16 (95% CI: −0.50 to 0.29; 44 trials). Correlation between the diagnostic yield and cancer mortality was −0.02 (95% CI: −0.72 to 0.45) for bowel ( n = 11) and −0.32 (95% CI: −0.83 to 0.19) for breast cancer ( n = 11). Conclusions For cancer screening RCTs, neither early-stage cancer incidence, the proportion of screen-detected cancers nor diagnostic yield of screening demonstrated a reliable correlation with cancer mortality.