The MRI targeted biopsy (MRI-TBx) may increase the detection rate of clinically significant cancer (csPCa) in candidates for re-biopsy. However, there will be several patients in whom MRI is contraindicated. In this retrospective study we assessed the ability of combination of PDS guided biopsies (PDS-TBx) and modified SBx to substitute MRI-TBx. 154 men with persistently elevated PSA were referred for re-biopsy. Our protocol included a combination of MRI-TBx, DPS-TBx and modified SBx with additional biopsies from anterior lateral horns and anterior aspects of apex. MRI findings were defined as suspicious lesions (MRI-SL) and highly suspicious lesions (MRI-HL), based on PIRADS scale. In 40 patients csPCa was detected. While, MRI diagnosed csPCa in 36 patients (23%, n-36/154): 25% and 92% of biopsies targeted to the MRI- SL and MRI-HSL confirmed csPCa. Thirty-eight PDS hypervascular areas were found, while csPCa was diagnosed in 84% of these lesions, or in 28 patients (18%, n-28/154). SBx detected csPCa in 34 cores or in 21 patients (13%, n – 21/154). SBx missed cancers in the in the anterior aspect of middle gland. Combination of PDS-TBx + SBx detected csPCa in 35 (88% of csPCa) patients. Strongest predictors for the csPCa presence were MRI-HSL, PDS’ lesions and biopsies from anterior aspect that included apex, mid gland and anterior lateral horns (p < 0.001 and p-0.008, respectively). The combination of PDS-TBx + SBx may miss 15% of csPCa detected by MRI. However, it can detect additional 10% of csPCa that were missed by MRI. To improve the accuracy of this combination, the anterior aspect of middle gland should be also included in the modified SBx. These changes in combination can make it helpful in candidates for re-biopsy who cannot undergo MRI.