Prospective evaluation of the role of imaging techniques and TMPRSS2:ERG mutation for the diagnosis of clinically significant prostate cancer.

Objectives: To test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa). Materials and methods: This is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with >=1 suspicious lesion (PI-RADS>2) at mpMRI or PR-IMUS >2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone. Results: The cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83. Conclusions: T2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role.