In modern practice, several reflexive biomarker assays, most notably the 4Kscore, enhance risk stratification for clinically significant prostate cancer (Grade Group ≥ 2). However, the 4Kscore may overestimate or underestimate risk in men with large prostates, as its algorithm incorporates PSA and other kallikrein isoforms alongside age, DRE, race, and biopsy history. To address this, our group investigated whether adjusting the 4Kscore by prostate volume could further improve its diagnostic performance.
We retrospectively reviewed 3,150 men who underwent 4Kscore testing between 2014 and 2024. After excluding those without prostate MRI, on active surveillance, or lacking biopsy within six months, 1,983 men remained. We calculated 4K Density (4Kscore ÷ prostate volume), paralleling PSA Density while leveraging MRI-based volumetrics for precise gland measurement. On receiver operating characteristic (ROC) analysis, 4K Density achieved an AUC of 0.81 for predicting clinically significant (GG2+) prostate cancer, outperforming the unadjusted 4Kscore (0.76), PSA Density (0.76), and total PSA (0.58). The improvement was most pronounced in men with intermediate (30-70cc) and large prostate volumes (≥ 70 cc).
While limited by retrospective design and inclusion of men proceeding to biopsy, these results suggest that adjusting biomarker interpretation for prostate volume can meaningfully improve specificity. 4K Density offers a simple, cost-free refinement that may help clinicians interpret 4Kscore results more accurately in men with large glands, reducing unnecessary biopsies and aligning with precision-screening principles. Prospective multicenter validation will be essential to confirm these findings and guide clinical integration of 4K Density.
Written by: Timothy Guerard, Joao G. Porto, Thomas Fekete, Omri Nativ, Gareth Reid, Adam Williams, Jonathan Ryan, Kevin Zhou, Elena Cortizas, Pedro Freitas, Archan Khandekar, Bruno Nahar, Chad Ritch, Mark Gonzalgo, Dipen J. Parekh, Sanoj Punnen
- University of Miami, Desai Sethi Urology Institute, Miami, Florida
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