Moving the Needle: Integrating Available Risk Stratification Tools for Optimizing Diagnosis of Prostate Cancer

Multiparametric MRI (mp-MRI) has significantly altered the diagnostic approach for prostate cancer (PCa) over the past decade. Landmark studies have shown that incorporating mp-MRI into the pathway from elevated PSA to prostate biopsy enhances the detection of clinically significant PCa (csPCa, ≥GG 2) while reducing the detection of clinically insignificant PCa (GG 1). This shift has helped mitigate the issues of overdiagnosis and overtreatment to some extent. In parallel, there has been development in promising biomarkers aimed at the same goal. Notable examples include the Prostate Health Index, 4K score, ExoDx Prostate IntelliScore, and SelectMDx. These biomarkers aid in determining whether a patient with an elevated PSA should proceed to prostate biopsy, mirroring the role of mp-MRI. The logical next question then is the potential added value of combining these diagnostic methods. To date, no prospective studies have been conducted to evaluate the combined utility of mp-MRI and these biomarkers. However, some retrospective studies, such as the present one by Wang et al,1 have explored this question. In their study, the authors demonstrate that a 4K score of ≥ 7.5% (alongside mp-MRI) correlates with a higher rate of acceptance by the patients to pursue a prostate biopsy. Although this investigation provides insight into the practical application of the test and illustrates its real-world implications, it leaves certain questions unaddressed, such as the exact improvement in cancer detection rates—owing to the study's retrospective nature and the fact that 30% of the study sample did not undergo biopsy, this question could not be answered; and the performance of the test in patients with Prostate Imaging-Reporting and Data System (PI-RADS) 1 to 2 lesions—which included too few patients to draw definitive conclusions. An intriguing retrospective study in this regard by Falagario et al highlighted the value of using a 4K score in patients with negative mp-MRI. By applying a threshold of ≥ 18% to perform prostate biopsy in patients with PIRADS 1 to 2 lesions, they showed a reduction in the likelihood of missing csPCa from 12% (if no biopsy) to 2.7%, while reducing the biopsy rate by ∼25%.2,3 These data suggest that these diagnostic tools could provide complementary information. While that may be the case, it is important to recognize that although both biomarkers and mp-MRI assist in risk stratifying patients with elevated PSA, mp-MRI also offers additional critical information, such as lesion location and prostate/pelvic anatomy, which are valuable for targeted biopsy and subsequent surgical/radiation or focal therapy treatment planning. Therefore, it is likely that mp-MRI will continue to be the preferred initial test for patients with elevated PSA. The clinical and economic benefits/trade-offs of using biomarkers as secondary tests after mp-MRI assessment warrant exploration in prospective trials. FUNDING None. CONFLICTS OF INTEREST None of the authors have any relevant disclosures, and none of the authors have any financial or non-financial interests that may be relevant to the submitted work.