Introduction and objectives:
The aim of our study was to evaluate the clinical management, follow up strategy and/or therapeutic approach in men with a negative multiparametric MRI (mpMRI)-TRUS targeted prostate biopsy (TB) with or without a contextual standard systematic 12-cores biopsy (SB).
Material and methods:
Between January 2015 and March 2019 we submitted to TB patients with clinical suspicion of prostate cancer (PCa) and a suspicious area (index lesion) at mpMRI (1.5 T magnet with endorectal coil). Patients were stratified in three groups: those with negative TB and a negative contextual SB (Group 1); patients with negative TB alone as SB was not performed in that same session (Group 2); men with negative TB and a contextual positive SB for PCa (Group 3).  In group 1 and 2 we evaluated the PSA trend during follow up and the results of further diagnostic procedures (including repeat mpMRI, TB and SB) in case of persistent suspicion of PCa in order to evaluate the clinical reliability of a negative TB. Finally, we reported the therapeutic approach adopted in patients in group 3.
Results:
Overall, 413 patients underwent fusion TB and 141 (34%) were found to be negative at pathological examination. Table 1 depicts overall patients’ characteristics. Non-statistical differences were observed between the three groups concerning age, PSA level, PSA density, suspected lesion’s size, location and PIRADs v2 score. Biopsy naïve patients were significantly lower in group 2 compared to group 1 and 3 (19.5% vs 55.6% and 35.8%, respectively; p<0.001).  Table 2 shows that PSA had no significant changes at last follow up (median follow up time of 10 months) in group 1 and group 2 patients. Overall, 9 patients (9.4%) repeated mpMRI within the follow-up interval, which resulted negative in 5 (55.6%) cases and it detected a suspicious index lesion in 4 cases (2 PIRADS v2 score 3, and 2 PIRADS v2 score 4 lesions). During follow up, 6 patients were submitted to re-biopsy (2 SB, 3 TB and 1 TB with contextual SB): 1 case resulted positive for PCa Gleason score 3+3 at systematic cores. In group 1 and 2, BPH surgery was performed in 5 cases, all resulted in a benign histology. Figure 2 resumes our therapeutic approach in patients with a negative TB and a contextual positive SB (Group 3): overall, 57.1% of patients were enrolled under AS or watchful waiting protocol, 39.3% were submitted to active radical treatment (radical prostatectomy in 28.6% and radiotherapy in 10.7%) and 3.6% of patients were scheduled for ADT.

Conclusion
Our study shows that a negative TB (with or without a contextual negative SB), can be clinically reliable for low risk to miss PCa diagnosis. BPH surgery can be performed with low risk of incidental PCa findings. SB continues to play a key role in PCa detection, as almost 40% of patients with a negative TB and a positive SB needed radical treatment.

THE IMPACT OF A NEGATIVE FUSION TARGETED BIOPSY: CLINICAL FAITH AND MANAGEMENT AT SHORT TERM FOLLOW UP.