Prostate-Specific Antigen Screening and Overdiagnosis in Prostate Cancer: A Systematic Review and Meta-Analysis
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Abstract
Background: Prostate cancer is the most frequently diagnosed malignancy among men. Screening strategies aimed at
reducing prostate cancer–related mortality have raised concerns about overdiagnosis—defined as the detection of cancers that
would not cause symptoms or death during a patient’s lifetime—and subsequent overtreatment. This review systematically
evaluates whether PSA-based screening primarily enables early detection or contributes to clinically relevant overdiagnosis.
Methods: Following PRISMA guidelines, randomized controlled trials and cohort studies enrolling men aged ≥ 40 years
without prior prostate cancer were included. Studies compared PSA-based screening with no screening or alternative
strategies. PubMed, Web of Science, and Scopus were searched from 2015 onward. Risk of bias was assessed using RoB2 for
randomized trials and the Newcastle–Ottawa Scale for cohort studies. Primary outcomes included prostate cancer diagnosis,
overdiagnosis, prostate cancer–specific mortality, and overall mortality.
Results: Thirteen studies enrolling men aged 45–74 years, with follow-up ranging from 2 to 22 years and sample sizes
from 4,276 to 415,357, were included. Biopsy-related complications were infrequent (≤2%), and MRI-guided biopsy was
associated with fewer infectious complications compared with standard transrectal biopsy. Overdiagnosis estimates varied
widely across studies; however, the pooled estimate was not statistically significant (RR 1.56 [95% CI 0.65–3.79]). PSA
screening did not reduce overall mortality (RR 0.99 [95% CI 0.88–1.11]). Prostate cancer–specific mortality was modestly
reduced, with pooled results borderline significant (IRR 0.87 [95% CI 0.76–1.00]). Substantial heterogeneity and risk of
bias across studies limited the certainty and generalizability of pooled estimates.
Conclusion: PSA-based screening is associated with a modest reduction in prostate cancer–specific mortality without an
improvement in overall survival. Lower overdiagnosis rates observed in more recent, risk-adapted screening strategies
highlight the importance of shared decision-making and support the integration of modern diagnostic tools to minimize harms.
Further well-designed, representative trials are needed to define optimal screening pathways across diverse populations