OBJECTIVES: To test the feasibility of combining percentage prostate-specific antigen (PSA) reduction and multiparametric magnetic resonance imaging (mpMRI) to determine the clinical scenario in which follow-up biopsy could be avoided after focal therapy (FT) with high-intensity focused ultrasound (HIFU) for prostate cancer. METHODS: We reviewed 90 men treated with FT. Percentage PSA reduction was calculated by PSA nadir within postoperative 6 months. mpMRI was arranged at postoperative 6 months, followed by routine biopsy. Logistic regression analyses were performed to identify predictors for clinically significant prostate cancer (csPC) on follow-up biopsy. Receiver operating characteristic curve analysis was done to assess the area under the curve (AUC). The diagnostic performance of percentage PSA reduction and mpMRI to predict csPC was also calculated. RESULTS: Eight patients had csPC recurrence. Percentage PSA reduction and Prostate Imaging-Reporting and Data System (PI-RADS) ≥ 3 at postoperative 6 months were predictors for csPC (p = 0.033 and p = 0.02, respectively). The AUC of mpMRI, percentage PSA reduction, and their combination were 0.95, 0.816, and 0.982, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSA reduction <
70% and PI-RADS ≥ 3 to predict csPC were 87.5%, 69.5%, 21.9%, 98.3%, and 87.5%, 96.3%, 70%, 98.8%, respectively. Using the criteria of PSA reduction <
70% or PI-RADS ≥ 3 to determine biopsy candidates could avoid 60% of biopsies, without missing csPC. CONCLUSION: For patients whose PSA reduction >
70% and PI-RADS <
3, we suggested avoiding routine biopsy at 6 months after FT with HIFU.