Dottorato in TECNOLOGIE BIOMEDICHE INNOVATIVE IN MEDICINA CLINICA

Titolo della tesi: SelectMDx and Thymidine kinase 1 (TK1) - novel biomarkers for the diagnosis and follow-up in early-stage and advanced prostate cancer

Objective To examine the performance of SelectMDx urinary biomarker in the initial diagnosis of PCa and clinically significant PCa (csPCa) on prostate biopsy (pBx), and the role of TK1 as possible serum prognostic biomarker for PCa and treatment response in early-stage and advanced prostate cancer (PCa) patients. Materials and Methods Men with a clinical suspicion of PCa underwent SelectMDx prior to pBx; SelectMDx diagnostic performance in predicting PCa and csPC at pBx has been assessed as sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). For TK1 evaluation, men without PCa (controls), non-metastatic PCa (nmPCa) and metastatic PCa (mPCa) cases have been included; TK1 baseline samples were obtained, as well as after and during therapies. Results 130 subjects underwent SelectMDx prior to pBx 51 (39.2%) cases were diagnosed with PCa, of whom 28 (54.9%) were csPCa. SelectMDx showed sensitivity, specificity, PPV, and NPV of 90.2%, 72.2%, 67.6% and 91.9%, and of 92.9%, 58.8%, 38.2% and 96.8% in predicting PCa and csPCa at pBx, respectively. For TK1 analysis, 89 men were included as PCa cases (nmPCa= 53 and mPCa= 36) and compared with 40 controls. At baseline, median TK1 levels varied from 0.23 (IQR 0.18-0.31) in the control group to 0.30 (IQR 0.24-0.36) in nmPCa group and 0.33 (IQR 0.29-0.44) in mPCa group. Longitudinal analyses on variations from baseline to different follow-up post-treatment intervals showed no statistically significant differences. Conclusions According to our analyses, SelectMDx revealed to be a good predictor of PCa and csPCa detection at pBx; TK1 levels varied among groups, and after and during therapies, yet with no significant differences, suggesting a limited role as biomarker for the follow-up of PCa patients.