Objective — to investigate structural changes in the tumor and nontumor tissues of the prostate in patients with its cancer (PC) after treatment with high-intensity focused ultrasound (HIFU) in combination with androgen deprivation to clarify criteria for evaluating the efficiency of treatment. Subject and methods. Comparative morphological, immunohistochemical, and morphometric analyses were carried out to examine 253 pre- and postoperative biopsy specimens, as well as transurethral resection specimens from 32 patients with localized PC and with or without a local recurrence within 3 years after a HIFU session. Results. HIFU ablation was accompanied by coagulation necrosis and progressive pancreatic fibrosis with complete tumor regression or by a reduction in the number of positive columns (by an average of 58%) in cases with recurrence. An inverse relationship was found between the degree of a reduction in the nontumor parenchyma in the control specimens and the probability of a recurrence — a less than 20% reduction in the non-tumor glands corresponded to a 3.4-fold increased risk of tumor progression. The development of recurrence was associated with less differentiated PC (GS ≥4+3) and the presence of cribriform structures in the pretreatment samples. Combined androgen deprivation as the maximum blockade was associated with the most pronounced signs of therapeutic pathomorphism, with a reduction of the microcirculatory bed in the focus of residual tumor, and a decrease in the frequency of local progression. Conclusion. Neoadjuvant hormone therapy contributes to the enhanced efficiency of HIFU treatment for PC. A less than 20% reduction in nontumor parenchyma volumes in the control biopsy specimens may indicate insufficient ablation in pancreatic tissue and serve as a marker for increased risk of local progression.