Introduction: Although adoption of new biomarkers and MRI has become widespread, their utility when deciding to biopsy is unclear. We aim to evaluate and compare the 4K score, SelectMDx, ExoDx and their added value when combined with prostate MRI in the detection of high-grade prostate cancer (HG PCa) and avoidance of unnecessary biopsies.
Methods: Patients referred for consideration of prostate biopsy at UCSF between 2016-2019 were enrolled and had either 4K, SelectMDx or ExoDx testing with or without MRI. Logistic regression and AUC were used to determine the performance of each biomarker in detecting HG PCa (defined as Gleason grade (GG) 3+4 or higher). In the subgroup of patients that underwent biopsy, with PSA 2.5-10 ng/mL and negative DRE, we determined the number of avoided unnecessary biopsies (with GG 3+3 cancer or no cancer) and missed HG PCa for each biomarker with or without MRI.
Results: A total of 896 patients were enrolled, 457 were biopsied and 651 had an MRI. Mean age was 65.5 years, median PSA was 6.32 ng/mL. Logistic regression showed that having an abnormal biomarker score or PI-RADS 4/5 on MRI was strongly associated with finding HG PCa: 4K OR 12.9 (CI 4.58-36.1), ExoDx OR 14.7 (CI 3.31-65.3), SelectMDx OR 3.62 (CI 1.44-9.11), P4/5 OR 6.20 (CI 3.93-9.79), TRUS =T2a OR 4.33 (CI 2.78-6.75), PSAD >0.15 OR 4.01 (CI 2.59-6.20), p <0.01). 4K, ExoDx and P4/5 had the highest AUC for detecting HG PCa (4K AUC 0.807, ExoDx AUC 0.848, SelectMDx AUC 0.679, P4/5 AUC 0.848, p <0.01). Combining biomarker with P4/5 on MRI increased the AUC for detecting HG PCa (‘4K and P4/5’ AUC 0.868, ‘ExoDx and P4/5’ AUC 0.876, p <0.01, ‘SelectMDx and P4/5’ AUC 0.795, p =0.06). In the biopsy subgroup, a normal 4K or ExoDx test missed only 4-5% HG PCa and avoided 14-20% unnecessary biopsies. Combining MRI with ExoDx or 4K missed 0-1.43% HG PCa but avoided only 7-9% unnecessary biopsies (Table 1).
Conclusions: 4K and ExoDx outperformed MRI and SelectMDx but combining the biomarkers with MRI resulted in the best predictive ability for detecting HG PCa. Negative MRI avoided more biopsies than a normal 4K or ExoDx but missed more aggressive cancers. Our data suggest that MRI alone is not sensitive enough to detect all HG PCa and that 4K or ExoDx testing alone could be sufficient when deciding to proceed with biopsy. Source of
Funding: University of California, San Francisco, Department of Urology