AbstractRationale and objectivesThe study aims to propose an optimal workflow in patients with a PI‐RADS 3 (PR‐3) assessment category (AC) through determining the timing and type of pathology interrogation used for the detection of clinically significant prostate cancer (csPCa) in these men based upon a 5‐year retrospective review in a large academic medical center.Materials and methodsThis United States Health Insurance Probability and Accountability Act (HIPAA)‐compliant, institutional review board‐approved retrospective study included men without prior csPCa diagnosis who received PR‐3 AC on magnetic resonance (MR) imaging (MRI). Subsequent incidence and time to csPCa diagnosis and number/type of prostate interventions was recorded. Categorical data were compared using Fisher's exact test and continuous data using ANOVA omnibusF‐test.ResultsOur cohort of 3238 men identified 332 who received PR‐3 as their highest AC on MRI, 240 (72.3%) of whom had pathology follow‐up within 5 years. csPCa was detected in 76/240 (32%) and non‐csPCa in 109/240 (45%) within 9.0 ± 10.6 months. Using a non‐targeted trans‐rectal ultrasound biopsy as the initial approach (n= 55), another diagnostic procedure was required to diagnose csPCa in 42/55 (76.4%) of men, compared with 3/21(14.3%) men with an initial MR targeted‐biopsy approach (n= 21); (p< 0.0001). Those with csPCa had higher median serum prostate‐specific antigen (PSA) and PSA density, and lower median prostate volume (p< 0.003) compared with non‐csPCa/no PCa.ConclusionMost patients with PR‐3 AC underwent prostate pathology exams within 5 years, 32% of whom were found to have csPCa within 1 year of MRI, most often with a higher PSA density and a prior non‐csPCa diagnosis. Addition of a targeted biopsy approach initially reduced the need for a second biopsy to reach a for csPCa diagnosis. Thus, a combination of systematic and targeted biopsy is advised in men with PR‐3 and a co‐existing abnormal PSA and PSA density.