Evaluating 4Kscore's Role in Predicting Progression on Active Surveillance for Prostate Cancer Independently of Clinical Information and PIRADS Score

Active surveillance (AS) has become an increasingly preferred approach for men with low-risk and select intermediate-risk prostate cancer, offering a way to delay or avoid the side effects of treatment. However, the intensity and invasiveness of surveillance protocols for disease progression remain burdensome for patients with prostate cancer. Our study assessed the role of the 4Kscore, a blood-based four-kallikrein biomarker, as a potential tool to enhance the monitoring of patients on AS within an MRI-based protocol.

We found that the 4Kscore was significantly associated with cancer progression both at the confirmatory biopsy and subsequent surveillance biopsies. Importantly, a baseline 4Kscore ≥20% was predictive of grade progression at confirmatory biopsy, while an elevated score on subsequent visits predicted progression during surveillance biopsies. This suggests that the 4Kscore may offer valuable information that can refine risk assessments beyond the initial MRI and clinical risk categorization.

Our study contributes new insights by exploring the 4Kscore's utility in the context of an MRI-driven AS protocol. Although MRI is a key component of AS, it cannot yet replace the need for biopsies, partly due to its variability in interpretation and dependence on radiologist expertise. Hence, the 4Kscore serves as an objective biomarker, providing a standardized means of assessing risk regardless of MRI quality or availability. This could be especially useful for centers with lower MRI volume or limited access.

One of the significant takeaways from our study is the consistent predictive value of a 4Kscore cutoff of 20% over the course of follow-up. The 4Kscore’s stability in predicting disease progression over multiple surveillance biopsies provides an additional layer of reassurance that could allow physicians to safely reduce the frequency of biopsies in men on AS. We noted that our per-protocol definition of progression includes both grade and volume, but our results emphasized the predictive strength of the 4Kscore specifically for grade progression—a clinically more important marker indicating a change in tumor biology rather than just sampling variability.

While MRI continues to be the gold standard for visualizing the prostate, biomarkers like the 4Kscore may complement imaging to better risk stratify patients and reduce the burden of testing. The advantage of biomarkers may be especially helpful in situations when MRI is not available or possible or when additional risk stratification is desired prior to re-biopsy for patients on AS. Our findings highlight the value of the 4Kscore as an independent predictor of prostate cancer progression in an MRI-based AS protocol. By offering this additional non-invasive risk stratification tool, the 4Kscore can help create a more patient-centered approach to prostate cancer management.

Biomarkers continue to be an exciting frontier to reduce the burden of surveillance and provide additional information for men low-risk prostate cancer. Our study demonstrating that 4Kscore independently predicts grade progression holds promise for biomarkers to be an integral part of surveillance protocols to improve outcome for men on AS.

Written by: Jamie Thomas,¹ Helen Y. Hougen,² Sanoj Punnen¹

Desai Sethi Urology Institute, University of Miami Miller School of Medicine and Sylvester Cancer Center, Miami, FL, USA
University of Iowa Hospitals and Clinics, Department of Urology, Iowa City, IA, USA

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