INTRODUCTION AND OBJECTIVE: The overall diagnostic yield of clinically significant prostate cancer (csPCa) in non-targeted biopsies in men with a suspicious mpMRI is reported to be 1 to 11%. The aim of this multi-centre study was to evaluate non-targeted prostate biopsies when performed alongside MRI-targeted biopsies, in terms of direct cost and marginal analysis (MA), pathologist reporting and MDT reviewing time. METHODS: A prospective online cancer pathway registry of 1,719 consecutive patients (Apr/2017-Oct/2019). MA defined as cost to diagnose one additional case of csPCa. reference cost of GBP£119/biopsy. Pathologist reporting and tumour board reviewing time of 8 minute/biopsy and 1 minute/biopsy, respectively, were used. Patients were advised transperineal biopsy if MRI score was 4-5 or 3 with PSA-density >/=0.12. csPCA was defined as Gleason >/=3+4. RESULTS: Mean age, median PSA and median prostate volume 65.7yrs (SD 8.5), of 6.7 (IQR 4.9-9.9) ng/ml and 50cc (IQR 35-75), respectively. 846 (49.2%) underwent biopsy with csPCa identified in 51.4% (435/846). csPCa was exclusively present in non-targeted prostate biopsies (i.e targeted biopsies had no cancer) in 2.5% (16/638). Direct cost of non-targeted negative or insignificant PCa was at £74,018.00 with 4,976 minutes of pathologist reporting and 622 minutes of tumour board reviewing time required. MA reported average cost per targeted and non-targeted case was £246.89 and £602.57, respectively. Marginal cost per case was £246.89 for targeted and £9,013.65 for exclusively non-targeted biopsy csPCa. CONCLUSIONS: Non-targeted biopsies performed in an MRI targeted-biopsy pathway have large direct and marginal costs per case. These consume valuable pathologist time but confer diminishing marginal benefit.Source of Funding: Imperial College Healthcare Charity