Multivariable test detects more significant prostate cancers than PSA alone

Clinical takeaway: After PSA-based screening, broader risk assessment may help clinicians decide who truly needs MRI and possible biopsy. Combining PSA with biomarkers, genetics, and clinical factors improved detection of clinically significant prostate cancer without meaningfully increasing false-positive results.

Prostate cancer screening remains challenging because prostate-specific antigen (PSA) testing can miss clinically significant cancers while also prompting biopsies for findings that may never become clinically important. A population-based screening analysis suggests that combining PSA with additional risk factors may offer a better balance between identifying higher-risk cancers and avoiding unnecessary downstream testing.

Researchers evaluated a multivariable screening tool that combines PSA level, plasma protein biomarkers, polygenic risk, and clinical factors into a single risk score. The analysis included 12,670 men aged 50 to 74 years in Sweden who underwent both PSA testing and the multivariable risk assessment.

Men with abnormal screening results, defined as PSA ≥3 ng/mL or a risk score ≥11, were randomly assigned to systematic biopsy or MRI with systematic and targeted biopsy for lesions with a Prostate Imaging Reporting and Data System score of 3 or higher. Prostate cancer diagnoses over two years were identified through linkage to the Swedish National Cancer Register.

Overall, 443 men, or 3.5%, were diagnosed with clinically significant prostate cancer, defined as grade group 2 or higher.

The multivariable tool detected more clinically significant cancers than PSA alone. Sensitivity was 90% with the risk score compared with 74% with PSA. The false-negative rate was also lower, at 10% compared with 26% for PSA.

Specificity was similar between the two approaches, at 89% with the risk score and 90% with PSA. False-positive rates were also comparable, at 11% and 10%, respectively.

In decision curve analysis, the multivariable approach provided greater net clinical benefit than PSA across a range of biopsy thresholds, driven mainly by fewer missed clinically significant cancers. The findings support further development of risk-adapted screening strategies that use more than PSA alone to guide decisions about MRI and biopsy.

Longer follow-up and validation in more diverse populations are needed before this type of screening strategy can be broadly incorporated into clinical practice.

Source: Palsdottir T, et al. 2026 June 23. Ann Intern Med. Stockholm3–magnetic resonance imaging population-based prostate cancer screening study: Two-year follow-up