Abstract Background Studies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44–50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels. Methods PSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmö Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years. Results Compared with biennial screening for ages 45–69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8–47.0% fewer tests (range between models), 0.9–2.1% fewer overdiagnoses, and 3.1–3.8% fewer lives saved. Stopping screening when PSA was less than 1.0 ng/mL at age 60 years and older led to 12.8–16.0% fewer tests, 5.0–24.0% fewer overdiagnoses, and 5.0–13.1% fewer lives saved. Differences in model results can be partially explained by differences in assumptions about the link between PSA growth and the risk of disease progression. Conclusion Relative to a biennial screening strategy, PSA-stratified screening strategies investigated in this study substantially reduced the testing burden and modestly reduced overdiagnosis while preserving most lives saved. Further research is needed to clarify the link between PSA growth and disease progression.

中文翻译：

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基于前列腺特异性抗原的前列腺癌风险分层筛查的终生益处和危害

摘要 背景在瑞典人群中进行的研究表明，44-50 岁和 60 岁前列腺特异性抗原 (PSA) 水平最低的男性未来因前列腺癌发生远处转移或死亡的风险非常低。本研究调查了按 PSA 水平分层的筛查策略的益处和危害。 方法将前列腺癌进展、检测和死亡率的两种微观模拟模型的 PSA 水平和诊断模式与马尔默预防项目的结果进行比较，该项目存储血清并跟踪随后的前列腺癌诊断 25 年。这些模型预测了 PSA 分层筛查策略与 45 岁至 69 岁每两年一次筛查的危害（检测和过度诊断）和益处（挽救生命和延长生命年）。 结果与 45-69 岁每两年筛查一次相比，延长 45 岁时 PSA 低于 1.0 ng/mL 男性的筛查间隔可减少 46.8-47.0% 的检查（模型之间的范围）、减少 0.9-2.1% 的过度诊断和获救的生命减少 3.1–3.8%。当 60 岁及以上 PSA 低于 1.0 ng/mL 时停止筛查，可减少 12.8-16.0% 的检查，减少 5.0-24.0% 的过度诊断，并减少 5.0-13.1% 的挽救生命。模型结果的差异部分可以通过对 PSA 增长与疾病进展风险之间联系的假设差异来解释。 结论相对于两年一次的筛查策略，本研究中调查的 PSA 分层筛查策略大大减轻了检测负担，并适度减少了过度诊断，同时保留了大多数已挽救的生命。需要进一步研究来阐明 PSA 增长与疾病进展之间的联系。