Introduction

The standard management for localized prostate cancer (PC) is radical treatment, such as radical prostatectomy or radiation therapy [1]. However, deterioration of urinary [2] and sexual function [3] is considered the main issue following radical treatment. With the development of diagnostic imaging technologies, individualization is being incorporated into cancer treatment, with each individual patient’s cancer condition being evaluated. The development of magnetic resonance imaging (MRI) has contributed to the accurate diagnosis of localization of PC, and has contributed to tailor-made treatment such as “focal therapy” that cures PC while preserving the anatomical structures related to urinary and sexual function [4]. Recently, high-intensity focused ultrasound (HIFU) has become a modality for focal therapy. HIFU is considered an attractive treatment modality for localized PC based on its long-term clinical results. HIFU is frequently used because it is appropriate for PC treatment in combination with three-dimensional millimeter-accurate planning in real-time trans-rectal ultrasound (TRUS) [5, 6] and MRI [7, 8], allowing for a distinct margin between the treated area and the adjacent untreated tissue without puncturing the prostate [9]. As no special construction work is required for installation, TRUS-guided HIFU is widely used as an ultrasound treatment device for localized PC, especially for focal therapy [10, 11].

History of high-intensity focused ultrasound for prostate cancer

The anti-cancer effect of HIFU was confirmed using rats with a subcutaneously implanted PC cell line [12, 13], and clinical application was evaluated using a canine prostate model [14,15,16]. Madersbacher et al. reported HIFU treatment for patients with PC as experimental focal ablation just before surgical resection of the prostate [9]. The temperature of the entire focal ablation area ranged from 70 to 98.6 °C during the ablation, as measured with a trans-peritoneal thermocouple, and the entire targeted area of the prostate was treated precisely [9]. Further, Beerlage et al. performed experimental hemi-ablation in nine patients 7–12 days before surgical resection of the prostate and confirmed the pathological changes (focal coagulation and necrosis) in the treated area [17].

Based on these preclinical studies, HIFU has been performed as a modality for whole-gland therapy for localized PC. Specifically, the 8-year disease-free survival rates for low-, intermediate-, and high-risk prostate cancer were 76–80.4%, 63–67.7%, and 57–69.6%, respectively, using the Phoenix American Society for Radiation Oncology (ASTRO) definition [5, 6]. Despite encouraging oncological outcomes, the occurrence of bladder outlet obstruction (BOO) in 6.5–41.1% [5, 18, 19] of patients who were treated with whole-gland HIFU was an issue that necessitated changing the treatment strategy with HIFU (Fig. 1).

Fig. 1
figure 1

Process of focal therapy with high-intensity focused ultrasound for a patient with localized prostate cancer. a The prostate cancer was diagnosed with magnetic resonance imaging-transrectal ultrasound fusion image-guided prostate biopsy. b The treatment probe, a built-in high-intensity focused ultrasound (HIFU) transducer, was inserted into the rectum. c HIFU was used to ablate the cancer diagnosed via biopsy

Full size image

In previous reports, MRI-trans-rectal ultrasound (TRUS) fusion image-guided biopsy [20], a representative technique of MRI-based targeted biopsy, and systematic biopsy achieved a high detection rate of PC, which was the largest or highest malignancy (Gleason scores) of PC in each patient. The development of localization of PC has contributed to tailor-made treatment such as “focal therapy” that cures PC while preserving the anatomical structures related to urinary and sexual function. HIFU has been reported as a representative modality for focal therapy. Five-year actuarial biochemical recurrence-free survival rates in patients in the low- and high-risk groups were 75% and 36%, respectively [21]. In a large multicenter prospective study with medium-term follow-up, the rates of failure-free survival (FFS)—which is defined as the avoidance of local salvage therapy with surgery or radiotherapy, systemic therapy, metastases, or PC-specific death—in the low-, intermediate-, and high-risk groups were 96%, 88%, and 84% in the 5-year follow-up [22] and 88%, 68%, and 65% in the 7-year follow-up [23], respectively. Regarding urinary function, continence was preserved in 80%–100% of patients after treatment [8, 21, 22, 24,25,26,27,28,29,30]. ED occurred in 14%–30% of patients [8, 21, 24, 26,27,28,29,30]. Urethral stricture has been reported to be less than 5%. In a clinical study evaluating the risk factors for contemporary deterioration in urinary function after focal therapy, there was a greater risk of urinary dysfunction with treatment in the bilateral anterior transition portion of the prostate than in the other portions during the treatment [31]. In a clinical study evaluating the risk factors for severe ED after focal therapy, pre-procedural lower condition of erectile function and treatment of the edge of the peripheral zone of the prostate in proximity to the neurovascular bundle were significant risk factors [32]. The results of these clinical studies will contribute to improving the informed consent process in patients considering receiving focal therapy with HIFU as a treatment for localized PC.

Approval as advanced medical care and future outlook

Recently, a multicenter prospective study of focal therapy with HIFU has been initiated to compare the oncological and functional outcomes of radical prostatectomy in pair-matched patients. Based on the clinical results of focal therapy and study design development, Japan’s Ministry of Health, Labour and Welfare approved focal therapy with HIFU as advanced medical care on February 1, 2023. Using the advanced medical care designation, a portion of medical expenses is covered by health insurance. This is the first approval for focal therapy in Japan. The clinical results of the multicenter prospective study will contribute to evaluation of the usefulness of focal therapy as one of the treatment options for patients with localized PC.