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Comparing S3M with a reflex threshold of 2 ng/mL with screening using the PSA test, S3M had increased effectiveness, reduced lifetime biopsies by 30%, and increased societal costs by 0.4%. Relative to the PSA test, the S3M reflex thresholds of 1, 1.5 and 2 ng/mL had ICERs of 170,000, 60,000 and 6,000 EUR/QALY, respectively. The S3M test was more cost-effective at higher biopsy costs. Prostate cancer screening using the S3M test for men with an initial PSA ≥ 2.0 ng/mL was cost-effective compared with screening using the PSA test alone. Prost