Introduction:

Prostate cancer (PCa) remains one of the most commonly diagnosed malignancies among men, with a wide spectrum of aggressiveness. A key clinical challenge is distinguishing patients who are likely to harbor clinically significant prostate cancer (csPCa) from those with indolent disease. The use of biomarkers has emerged as an essential tool to enhance risk stratification and guide biopsy decisions. The 4Kscore test, which integrates four kallikrein biomarkers with clinical variables, offers a personalized risk estimate for csPCa. In this study, we evaluated the long-term outcomes of men who underwent 4Kscore testing, focusing on different score cutoffs (≤5%, 5.1–≥10.1%) to assess their predictive value over a 10-year follow-up period.

Methods:

We retrospectively reviewed 113 men who underwent 4Kscore testing between 2014–2015 and had clinical follow-up data through 2025. Primary outcomes included prostate cancer diagnosis, Gleason grade group (GG), treatment, and prostate cancer-survival outcomes. Patients were stratified into three risk categories based on their 4Kscore level: low risk (≤5%), intermediate risk (5.1–10%) and high risk (≥10.1%).

Results:

Among 113 patients, 37 (33%) were low-risk, 17 (15%) intermediate-risk, and 59 (52%) high-risk by 4Kscore. At 10 years, csPCa rates were 11% in the low-risk, 36% in the intermediate-risk, and 44% in the high-risk groups. No cases of high-risk PCa were diagnosed in the low-risk 4Kscore group. In contrast, high-risk disease was identified in both the intermediate and high-risk groups, where patients in the high-risk category had a more than 5-fold increased risk of developing csPCa (p < 0.001) and nearly a 4-fold increased risk of high-grade disease (GG ≥4) (p < 0.001) compared to those in the low-risk group. In addition, conversion from active surveillance to definitive treatment was significantly higher in the high-risk group (46%) versus low-risk (8%) (HR 7.25). No cases of metastatic progression or prostate cancer–specific mortality were observed in the low-risk group over the 10-year follow-up. In contrast, all events of metastatic progression and the single prostate cancer specific death occurred exclusively in the intermediate and high-risk groups. (Table 1, Figure 1)

Conclusion:

This 10-year follow-up study supports the 4Kscore as a meaningful clinical tool for long-term risk stratification of prostate cancer. A low 4Kscore (≤5%) reliably identifies men at minimal risk of aggressive disease, enabling safe biopsy deferral and reduced overtreatment. Higher 4K score values predict greater incidence of csPCa, high-grade disease, need for definitive therapy, progression to metastatic disease and cancer specific mortality, underscoring its value in guiding personalized management and surveillance strategies. Future large-scale prospective studies are warranted to confirm these findings and refine risk thresholds

Funding: N/A