Validating fPSA Glycoprofile as a Prostate Cancer Biomarker to Avoid Unnecessary Biopsies and Re-Biopsies

SIMPLE SUMMARY: We have proved here that a magnetic bead-based assay using lectins can be effectively applied for glycoprofiling of free prostate specific antigen (fPSA). Such a glycan-based biomarker improves the detection of prostate cancer (PCa) in the PSA grey zone, the discrimination between clinically significant and insignificant cancer, and can significantly reduce the number of unnecessary prostate biopsies and re-biopsies, outperforming current second opinion tests such as percentage of fPSA (fPSA%) and the prostate health index (PHI). ABSTRACT: Background: To compare the clinical performance of a new PCa serum biomarker based on fPSA glycoprofiling to fPSA% and PHI. Methods: Serum samples from men who underwent prostate biopsy due to increased PSA were used. A comparison between two equal groups (with histologically confirmed PCa or benign, non-cancer condition) was used for the clinical validation of a new glycan-based PCa oncomarker. SPSS and R software packages were used for the multiparametric analyses of the receiver operating curve (ROC) and for genetic algorithm metaheuristics. Results: When comparing the non-cancer and PCa cohorts, the combination of four fPSA glycoforms with two clinical parameters (PGI, prostate glycan index (PGI)) showed an area under receiver operating curve (AUC) value of 0.821 (95% CI 0.754–0.890). AUC values were 0.517 for PSA, 0.683 for fPSA%, and 0.737 for PHI. A glycan analysis was also applied to discriminate low-grade tumors (GS = 6) from significant tumors (GS ≥ 7). Conclusions: Compared to PSA on its own, or fPSA% and the PHI, PGI showed improved discrimination between presence and absence of PCa and in predicting clinically significant PCa. In addition, the use of PGI would help practitioners avoid 63.5% of unnecessary biopsies, while the use of fPSA% and PHI would help avoid 17.5% and 33.3% of biopsies, respectively, while missing four significant tumors (9.5%).