Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

OBJECTIVE: To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. PATIENTS AND METHODS: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. RESULTS: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. CONCLUSIONS: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.

High-Intensity Focused Ultrasound (Sonablate®) for Prostate Cancer: Preliminary Outcomes in Taiwan.

PURPOSE: We reported preliminary outcomes of high-intensity focused ultrasound (HIFU) [Sonablate®] in the combination of transurethral resection of the prostate for localized prostate cancer in Taiwan. METHODS: Seventy-seven patients using Sonablate® HIFU for localized prostate cancer were enrolled in this study from April 2021 to December 2022. Prostate-specific antigen biochemical recurrence, International Index of Erectile Function (IIEF)-5 scores, International Prostate Symptom Score (IPSS), quality of life (QoL) scores, and postoperative complications were recorded during follow-up. RESULTS: Overall, 19.5% of patients were low-risk, 36.4% were intermediate-risk, and 44.1% were high-risk according to the D'Amico risk classification. The median follow-up was 12.09 ± 5.85 months, and the biochemical-free survival rates for the low-, intermediate-, and high-risk groups were 100% (15/15), 96.4% (27/28), and 79.4% (27/34), respectively. Four patients (5.2%) received salvage radiotherapy and all maintained biochemical-free survival. The mean IPSS and QoL scores before versus after HIFU were 10.4 versus 6.8 (p = 0.003) and 3.2 versus 3.0 (p = 0.096), respectively. There was no statistically significant change in preoperative and postoperative IIEF scores (20.6 vs. 19; p = 0.062) in patients who had an IIEF score of >15 at baseline and received nerve-sparing procedures (subtotal ablation). CONCLUSIONS: The results of Sonablate® HIFU in Taiwan indicated adequate short-term cancer control, excellent potency, and continence preservation. HIFU can achieve improvement of IPSS with low complication rates.

Long-term outcomes of whole gland high-intensity focused ultrasound for localized prostate cancer.

OBJECTIVES: To report the 10-year oncologic and functional outcomes of whole-gland HIFU as first-line treatment for localized prostate cancer (PCa). PATIENTS AND METHODS: Patients were retrospectively included between January 2005 and July 2018 from a prospectively maintained database at a single academic institution. No patient underwent androgen deprivation therapy prior to HIFU. Primary endpoint was biochemical recurrence-free survival (BRFS). Secondary oncological endpoints included salvage treatment-free survival (STFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: A total of 97 patients met our inclusion criteria and were included in the final analysis. According to D'Amico classification, the numbers of patients with low-, intermediate-, and high-risk disease were 38 (39.2%), 52 (53.6%), and 7 (7.2%). A total of 21 (21.6%) patients received salvage treatment at a mean of 4.1 years (± 2.8) after HIFU. The 10-year OS, CSS and BRFS rates were 91.8%, 100% and 40.3% in the overall cohort, respectively. In multivariate analysis, predictive factors for biochemical recurrence were intermediate-risk group (RR = 2.065; 95% CI 1.008-4.230; p = 0.047) and PSA nadir > 0.5 ng/mL (RR = 4.963; 95% CI 2.251-10.947; p < 0.001). Symptoms related to bladder outlet obstruction were the most frequently recorded adverse events. In multivariate analysis, positive biopsy on the prostatic apex was predictor of obstructive complications (RR = 3.2, 95% CI 1.092-9.476, p = 0.034). Only four patients developed severe urinary incontinence (> 1 pad/day). CONCLUSIONS: HIFU showed low PCa-specific mortality, but biochemical recurrence rates were highly variable among patients. Future studies are needed to improve patient selection.

Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience.

BACKGROUND: Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. OBJECTIVE: To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification. RESULTS AND LIMITATIONS: The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo >2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking. CONCLUSIONS: Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term. PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

High-intensity focused ultrasound for the treatment of prostate cancer: assessing location of failure after focal therapy in prostate cancer and review of histological characteristics and clinicopathologic correlates after treatment-a 5-year experience.

High-intensity focused ultrasound (HIFU) is a noninvasive treatment option used for localized prostate cancer or salvage surgery after failed radiation therapy. Histological changes in post-treatment needle biopsies are reviewed to better understand HIFU failures. Between 2016 and 2021, 50 patients with localized prostate cancer were enrolled and treated in this study. Of these, 10 patients underwent salvage therapy after radiation failure and 7 did not have post-treatment needle biopsies available for review and were excluded. Inclusion criteria included pathologically confirmed prostate cancer and clinical stage T1/T2 disease. We describe the histological changes in post-treatment needle biopsies as part of routine follow-up. Biopsies were examined for presence, distribution and extent of residual adenocarcinoma, Gleason score, and ablative tissue changes. A total of 33 patients underwent HIFU hemi-ablation treatment of localized prostate cancer as primary treatment with post-treatment biopsies available for review. The average mean age of the patients was 64 years (range, 52-81 years). The average PSA (prostate-specific antigen) level of the patients was 6.3 ng/mL (range, 2.4-14.7 ng/mL). The Gleason scores assigned in pretreatment prostate needle biopsies are as follows: 3 + 3 (1 case, 3%), 3 + 4 (21 cases, 64%), 4 + 3 (9 cases, 27%), and 4 + 4 (2 cases, 6%). In post-treatment needle biopsies, 33 cases (100%) showed variable degrees of fibrosis ranging from mild to moderate. Twenty-four of 33 cases (73%) showed necrosis usually associated with acute and/or chronic inflammation. Histological examination of benign glands revealed glandular heterogeneity including atrophy and basal cell hyperplasia. Eight cases (24%) had residual prostatic adenocarcinoma after treatment, of which 4 cases were assigned Gleason score: ≥3 + 4. In cases with residual adenocarcinoma, 8 cases (100%) showed nuclear enlargement, 5 cases (63%), cytoplasmic vacuolization, and 1 case (13%) showed nuclear pyknosis; otherwise, no discernible effects of treatment were seen. Morphological alterations included a spectrum of changes ranging from extensive coagulative stromal necrosis secondary to thermal injury to atrophic changes in benign prostatic tissue after HIFU treatment. Our findings also support the hypothesis that HIFU failure results from inadequate targeting rather than failure within a treated zone.

[High-intensity focused ultrasound for locally prostate cancer: An Afro-Caribbean single-center study]. / Ultrasons focalisés de haute intensité pour le traitement du cancer localisé de la prostate : étude mono-centrique caribéenne.

INTRODUCTION: High-intensity focused ultrasound (HIFU) has proved to be effective in the treatment of localized prostate cancer. The aim of this prospective study is to assess their first oncological and functional results in an Afro-Caribbean population. METHODS: From May 2018 to January 2020, 77 patients issued from French West Indies were included. Several treatments were carried out: whole-gland treatment hemi or focal ablation; in a primary setting (group I) or a salvage therapy (group II). PSA level was assessed at 2, 6, 9 and 12 months. MpMRI and post HIFU biopsy were performed between 6 and 9 months postoperatively. Continence, urinary end erectile functions were assessed by ICS, IPSS and IIEF scores. RESULTS: Groupe I included 71.2% patients, group II, 28.8%. The median age was 75.4 years [IQR 69.6-79.4]. The median follow-up was 8.3 months [IQR 3.5-12.25]. At inclusion, PSA was 7.7ng/ml [IQR 5.5-11.2] in group I, and 5.9ng/ml [IQR 4.4-7.9] in group II. In the whole population, there was 73.5% negative biopsies; 14.7% of the biopsies were positive in treated zone and 11.8% in non-treated zone. Regarding morbidities, urinary incontinence appeared in 7.5% and erectile dysfunction rate was 13.2%. CONCLUSION: Our study reveals the first experience of HIFU by Focal One® device in an Afro-Caribbean population. It seems to be a safe and reproducible treatment with acceptable oncological results and low genitourinary morbidity. Long term follow-up and a higher number of patients are necessary to validate these results.

A pilot study of the shapes of ablation lesions in the canine prostate by laser, radiofrequency and microwave and their clinical significance.

To explore the shape characteristics of ablation lesions created via laser ablation (LA), radiofrequency ablation (RFA) and microwave ablation (MWA) in canine prostates and the clinical significance of these characteristics, six adult male beagles were randomly assigned to the LA, RFA, and MWA groups. These ablations were performed with common parameters applied in clinical practice (LA, 3 W/1200 J; RFA and MWA, 30 W/120 s). One ablation lesion was created in each lobe of the prostate via the ablation technique, resulting in a total of twelve ablation lesions. Transrectal ultrasound (TRUS) was used as guidance during puncture and to monitor changes in the ablation lesions. Finally, the ablation efficacy was assessed using transrectal contrast-enhanced ultrasonography (CEUS), and the transverse diameter (TRD), anteroposterior diameter (APD) and longitudinal diameter (LD) of each ablation lesion were measured. The volume (V) and the ratio (R) value were calculated. R reflects the shape characteristic of the ablation lesion (the R value close to 1.0 indicates a more spherical shape). The R values of the ablation lesions were 0.89 ± 0.02, 0.72 ± 0.01, and 0.65 ± 0.03 for RFA, MWA and LA, respectively, and they were significantly different (P = 0.027). The volumes of the ablation lesions were 2.17 ± 0.10 ml, 1.51 ± 0.20 ml, and 0.79 ± 0.07 ml for MWA, LA and RFA, respectively, and they were also significantly different (P = 0.001). The three abovementioned thermal ablation techniques with common parameters in clinical practice can be used for ablation in the prostate. The shapes and volumes of the ablation lesions of the three techniques were varied: The RFA-created lesions had the lowest volumes and were more spherical in shape, demonstrating that RFA could be used for the treatment of relatively small lesions or tumours adjacent to vital organs. The MWA lesions had the largest size with a spherical shape, which could be advantageous for the ablation of tumours with relatively large sizes. The sizes of the ablation lesions created via LA were between those of RFA and MWA but presented more oval in shape, suggesting that this method is highly appropriate for the ablation of benign prostatic hyperplasia (BPH).

Evaluation of functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) procedure in men with primary localized, non-metastatic prostate cancer: results from the HIFU Evaluation and Assessment of Treatment (HEAT) registry.

OBJECTIVES: To assess change in functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. PATIENTS AND METHODS: In this multicentre study (2005-2016), 821 men underwent focal HIFU for localized non-metastatic prostate cancer. The patient-reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow-up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. RESULTS: Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow-up questionnaires, respectively. The mean age and prostate-specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was -0.03 (P = 0.02) and in IIEF (EF score) it was -0.4 (P = 0.02) at 1-2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak-free continence decreased from 77.9% to 72.8% (P = 0.06) and pad-free continence from 98.6% to 94.8% (P = 0.07) at 1-2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by -1.3 (P = 0.02), but mean IPSS change was +1.4 at 1-2 years (P = 0.03) and +1.2 at 2-3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was -0.2 at 1-2 years (P = 0.60) and -0.5 at 2-3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. CONCLUSION: A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.

Salvage high-intensity focused ultrasound for locally recurrent prostate cancer after low-dose-rate brachytherapy: oncological and functional outcomes.

OBJECTIVES: To evaluate the oncological and functional outcomes of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after low-dose-rate (LDR) brachytherapy. PATIENTS AND METHODS: Clinical phase II studies (2003-2015) included 50 consecutive patients with post-brachytherapy local recurrence treated by S-HIFU. S-HIFU was performed with post-external beam radiotherapy (EBRT) parameters and, since 2008, with specific post-brachytherapy parameters. Treatments were whole-gland ablation and, since 2009, hemi-ablation in cases of unilateral prostate cancer. The primary objective was to assess oncological outcomes: treatment failure-free survival, progression-free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) rates. The secondary objective was to evaluate adverse events, continence, and erectile function. Kaplan-Meier analysis estimated oncological outcomes. RESULTS: In all, 13 patients were treated with post-EBRT parameters, 37 with post-brachytherapy parameters, 35 with whole-gland treatment, and 15 with hemi-ablation. The median follow-up was 4.6 years. After S-HIFU, the median prostate-specific antigen level was 0.3 ng/mL. At 6 years, treatment failure-free survival, PFS, OS, CSS, and MFS rates were 41%, 45%, 93%, 98%, and 80%, respectively. Post-brachytherapy compared with post-EBRT parameters reduced Grade 2-3 incontinence (34% vs 62%, P = 0.015). Incontinence, bladder outlet obstruction and Grade ≥III complications were significantly reduced with hemi-ablation compared with whole-gland treatment (14% vs 54%, P < 0.001; 13% vs 46%, P = 0.03; 13% vs 63%, P = 0.001; respectively). Before S-HIFU, 25 patients had a five-item version of the International Index of Erectile Function score of ≥17, which was maintained in 48% at 12 months. CONCLUSION: S-HIFU for locally recurrent prostate cancer after LDR brachytherapy is associated with favourable survival rates at a price of significant morbidity. Dedicated post-brachytherapy parameters and hemi-ablation improve the safety of the treatment.

[Focal HIFU vs robot-assisted total prostatectomy: Functionnal and oncologic outcomes at one year]. / Traitement focal par HIFU versus prostatectomie radicale robot-assistée pour cancer de la prostate localisé : résultats carcinologiques et fonctionnels à 1 an.

OBJECTIVE: To analyse the functional and oncologic outcomes at one year of focal therapy with HIFU compared with total prostatectomy in patients with localised prostate cancer (PCa). PATIENTS AND METHODS: Retrospective and monocentric study from 2008 to 2014 comparing 2 cohorts of patients with localised PCa (T1/T2 clinical stage, Gleason score≤3+4=7 and PSA<15ng/mL), one treated by focal therapy (HIFU-F group), one by robot-assisted total prostatectomy (RATP group). Primary outcome was a trifecta defined as: absence of urinary incontinence, erectile function with sexual relations without treatment, negative PSA with negative surgical margins (RATP group) or negative biopsy cores (HIFU-F group). RESULTS: The 53 patients included in the "HIFU-F" group and the 66 patients in the "RATP" group were similar in terms of preoperative PSA, D'Amico risk group, erectile function but were different in terms of age, prostatic volume, length of cancer, Gleason score. Complication rate was not different. In multivariate analyse with propensity score, "HIFU-F" group achieved a better trifecta score than "RATP" group (OR=8,3, p=0,005). CONCLUSION: In case of low or intermediate risk localised PCa, "HIFU-F" group had better functional outcomes than initial learning curse "RATP" group, at one year. A long-term evaluation by a common endpoint is necessary to judge the oncological equivalence of both techniques. LEVEL OF EVIDENCE: 3.

A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer.

BACKGROUND: Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects. OBJECTIVE: To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%). INTERVENTION: Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality. RESULTS AND LIMITATIONS: The median follow-up was 56 mo (interquartile range [IQR] 35-70). The median age was 65 yr (IQR 61-71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2-10.0). FFS was 99% (95% confidence interval [CI] 98-100%) at 1 yr, 92% (95% CI 90-95%) at 3 yr, and 88% (95% 85-91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97-99%), 100%, and 99% (95% CI 97-100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up. CONCLUSIONS: Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects. PATIENT SUMMARY: In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.

Primary whole-gland ablation for localized prostate cancer with high-intensity focused ultrasound: The important predictors of biochemical recurrence.

OBJECTIVES: To identify predictive factors of biochemical recurrence for patients undergoing high-intensity focused ultrasound treatment for localized prostate cancer. METHODS: We retrospectively identified patients receiving whole-gland prostate ablation with high-intensity focused ultrasound for localized prostate cancer from 2009 to 2015. All the patients received pre-high-intensity focused ultrasound radical transurethral resection of the prostate. We included perioperative parameters as follows: age, preoperative prostate volume, stage of operation, initial prostate-specific antigen, T stage, postoperative prostate-specific antigen nadir, Gleason score, time to prostate-specific antigen nadir and the presence of prostate-specific antigen biochemical recurrence. Multivariable Cox regression and Kaplan-Meier analysis were used for investigating predictors of recurrence, and receiver operating characteristic analysis was used for the cut-off values of prostate-specific antigen nadir. RESULTS: Among 182 patients, 26.9% had prostate-specific antigen biochemical recurrence after high-intensity focused ultrasound during the median follow-up period of 32.21 months. Gleason score ≥7 (Gleason score 7, hazard ratio 2.877, P = 0.027), stage ≥T2b (T2b, hazard ratio 3.16, P = 0.027) and prostate-specific antigen nadir (hazard ratio 1.11, P < 0.001) were statistically significant, whereas there was no significance in prostate volume and initial prostate-specific antigen. We posit that a cut-off level of prostate-specific antigen nadir 0.43 ng/mL might be considered as an independent predictive factor for prostate-specific antigen biochemical recurrence in high-intensity focused ultrasound patients in multivariate analysis (P < 0.001, hazard ratio 7.39, 95% confidence interval 3.56-15.37), and created a new nadir-related prediction model for biochemical recurrence prediction. CONCLUSIONS: Postoperative prostate-specific antigen nadir of 0.43 ng/mL can be considered an important predictive factor for biochemical recurrence in primary whole-prostate gland high-intensity focused ultrasound treatment, and the nadir-related prediction model might provide a reference for early salvage treatment. Furthermore, Gleason score ≥7, stage ≥T2b might be associated with unfavorable outcomes, although prostate volume and higher initial prostate-specific antigen appear not to be associated with biochemical recurrence for the high-intensity focused ultrasound treatment.

Prospective Multicenter Phase II Study on Focal Therapy (Hemiablation) of the Prostate with High Intensity Focused Ultrasound.

PURPOSE: We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospective trial. MATERIALS AND METHODS: We performed a prospective, multicenter, single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO (Arbeitsgemeinschaft Urologische Onkologie) Study Protocol AP 68/11. Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging. Hemiablation was done using the Ablatherm® or the Focal One® device. The oncologic outcome was assessed by the salvage treatment rate, multiparametric magnetic resonance imaging and rebiopsy at 12 months. Functional outcome, quality of life, anxiety and depression were measured by validated questionnaires at baseline and every 3 months. RESULTS: Of the 54 recruited patients 51 completed 12-month or greater visits. Mean ± SD followup was 17.4 ± 4.5 months. Mean prostate specific antigen decreased from 6.2 ± 2.0 to 2.9 ± 1.9 ng/ml at 12 months (p <0.001). Biopsy at 12 months was positive for any prostate cancer and for clinically significant prostate cancer in 13 (26.5%) and 4 (8.2%) of the 49 patients, respectively. Posttreatment multiparametric magnetic resonance imaging had limited 25% sensitivity for clinically significant prostate cancer. Ten patients (19.6%) underwent salvage treatment. Potency was maintained in 21 of the 30 men who were potent preoperatively. There was no increase in incontinence. Quality of life, anxiety and depression did not change postoperatively. The study was limited by a short followup and the lack of a control arm. CONCLUSIONS: Focal therapy hemiablation is safe with little alteration of functional outcome. The oncologic outcome is acceptable on short-term followup. Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy. Focal therapy has no impact on posttreatment anxiety and depression.

Clinical comparison of the efficacy of three different bowel preparation methods on the infectious complications following transrectal ultrasonography-guided prostate biopsy in nursing practice.

AIMS AND OBJECTIVES: To assess the effects of three different bowel preparation methods on the incidence of infectious complications in patients who underwent transrectal ultrasonography-guided prostate biopsy. BACKGROUND: The standard bowel preparation protocol for prostate biopsy has not been established. DESIGN: A retrospective study in a single centre. METHODS: From January 2013-December 2015, the clinical records of 1,130 patients who underwent prostate biopsy were, respectively, reviewed. All the patients received metronidazole prophylaxis before biopsy. The patients were divided into three groups according to the bowel preparation methods: patients in Group A (n = 402) received only soapy enema; patients in Group B (n = 413) received polyethylene glycol; while patients in Group C (n = 315) received polyethylene glycol plus povidone-iodine enema. Infectious complications were classified as fever (>37.5°C), urinary tract infection and sepsis. The postoperative adverse events were also observed. RESULTS: The overall postbiopsy infectious complications were observed in 48 (4.25%) patients of all the cases, including 23 (5.72%) cases in Group A, 20 (4.84%) cases in Group B and five patients (1.59%) in Group C. There was significant difference among the groups (p = .018). In detail, these infectious complications included 22 (1.95%) cases of fever and 26 (2.30%) cases of urinary tract infection. No sepsis was observed among the total patients. The incidence of adverse events was 14.43% (58/402) occurred in Group A, 25.91% (107/413) in Group B and 26.67% (84/315) in Group C. The difference was statistically significant. CONCLUSIONS: Our study confirmed that combined preparation regimens of polyethylene glycol with povidone-iodine enema could significantly reduce the postbiopsy infection rate. Conventional soapy enema is associated with less adverse events. RELEVANCE TO CLINICAL PRACTICE: Findings of this study provide useful evidence-based information for healthcare professionals. The application of combined preparation regimens of polyethylene glycol with povidone-iodine enema resulted in better improvement in the prevention of postbiopsy infection.

Focal Therapy for Prostate Cancer with In-Bore MR-guided Focused Ultrasound: Two-Year Follow-up of a Phase I Trial-Complications and Functional Outcomes.

Purpose To report the safety profile and 2-year functional outcomes of in-bore magnetic resonance (MR)-guided focused ultrasound on single cancer foci in men with prostate cancer. Materials and Methods Ethics approval was obtained from the centralized institutional review board for this prospective single-arm study, and patients provided informed consent. Patients with untreated low-volume low-grade prostate cancer (clinical stage T2a or lower; Gleason score, 3+3; index tumor ≤10 mm3) underwent MR-guided focused ultrasound between July 2011 and February 2013. All patients underwent robotic transperineal mapping biopsy and multiparametric MR imaging. Only those with a maximum of two lesions smaller than 10 mm at mapping biopsy were included. Target areas were sonicated with real-time MR thermometry monitoring, excluding critical areas from the beam path. Serum prostate-specific antigen (PSA) and Expanded Prostate Index Composite (EPIC) scores were obtained at baseline and at 1, 3, 6, 12, 18, and 24 months and were plotted to observe their trend. Mean EPIC subdomain score changes at each serial time point were compared with the baseline score by using paired t tests (level of significance, P < .007). Repeat transperineal biopsy was performed at 6 and 24 months. Results Fourteen men (mean age, 62.8 years; median PSA level, 8.3 ng/mL) underwent treatment, with 12 men completing 2-year follow-up. A median reduction of PSA level by 2.9 ng/mL was observed at 6 months. Seven men had Clavien-Dindo grade 1-2 complications. There was a slight insignificant deterioration of EPIC urinary symptom score (mean increase of 7.8 points compared with baseline, P = .012) noted at 1 month, but it returned to baseline by 3 months. There was a trend to deterioration in sexual function score (mean decrease, 4.4 points; P = .04 [not significant]) that normalized at 3 months. There was no significant change in EPIC subdomain scores from baseline over the 24 months. At 6-month template biopsy, one man had cancer with a Gleason score greater than 6; at 24 months, three men had cancer with a Gleason score greater than 6. Conclusion MR-guided focused ultrasound is technically feasible for focal prostate ablation and appears to have a favorable early safety and functional profile. Further clinical trials are necessary to establish oncologic efficacy. © RSNA, 2017 Online supplemental material is available for this article.

Focal salvage high-intensity focused ultrasound in radiorecurrent prostate cancer.

OBJECTIVE: To assess short- to medium-term cancer control rates and side effects of focal salvage high- intensity focused ultrasound (HIFU). MATERIALS AND METHODS: A retrospective registry analysis identified 150 men who underwent focal salvage HIFU (FS-HIFU) (Sonablate 500) between November 2006 and August 2015. Metastatic disease was excluded by nodal assessment on the pelvic MRI, a radioisotope bone scan and positron-emission tomography (PET) imaging (choline-18F-fluorodeoxyglucose PET or choline PET-CT). In our current clinical practice, metastatic disease must be excluded by both choline PET and bone scan. Localization of cancer was carried out using multiparametric MRI of the prostate (T2-weighted, diffusion-weighted and dynamic contrast-enhanced imaging) with systematic or template prostate mapping biopsies. The primary outcome was a composite failure incorporating biochemical failure (BCF) and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer-specific death. The secondary outcome was BCF using the Phoenix-ASTRO definition (prostate-specific antigen [PSA] nadir + 2 ng/mL). We used Kaplan-Meier analysis and Cox proportional hazards regression to quantify the effect of the determinants on the endpoints. RESULTS: The mean (standard deviation [sd]) patient age at focal salvage HIFU was 69.8 (6.1) years and the median (interquartile range [IQR]) PSA pre-focal salvage HIFU was 5.5 (3.6-7.9) ng/mL. The median (IQR) follow-up was 35 (22-52) months. Patients were classified as having low- 2.7% (4/150), intermediate- 39.3% (59/150) and high-risk disease 41.3% (62/150) according to D'Amico classification, prior to focal salvage HIFU. Composite failure occurred in 61% of patients (91/150) and BCF occurred in 51.3% (77/150). The Kaplan-Meier composite endpoint-free survival (CEFS) rate at 3 years was 40% (95% confidence interval [CI] 31-50) for the entire group. Kaplan-Meier estimates of CEFS were 100%, 49% and 24% at 3 years in the low-, intermediate- and high-risk groups pre-salvage HIFU, respectively. The Kaplan-Meier biochemical disease-free survival (BDFS) rate at 3 years was 48% (95% CI 39-59) for the entire group. Kaplan-Meier estimates of BDFS were 100%, 61% and 32% at 3 years in the low-, intermediate- and high-risk groups pre-salvage HIFU, respectively. Complications included urinary tract infection (11.3%; 17/150), bladder neck stricture (8%; 12/150), recto-urethral fistula after one HIFU procedure (2%; 3/150) and osteitis pubis (0.7%; 1/150). CONCLUSION: Focal salvage HIFU conferred a relatively low complication and side effect rate. CEFS and biochemical control in the short to medium term were reasonable, especially in this relatively high-risk cohort, but still low compared with current whole-gland salvage therapies. Focal salvage therapy may offer disease control in men at high risk whilst minimizing additional treatment morbidities.

The PICTURE study: diagnostic accuracy of multiparametric MRI in men requiring a repeat prostate biopsy.

BACKGROUND: Transrectal prostate biopsy has limited diagnostic accuracy. Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE) was a paired-cohort confirmatory study designed to assess diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in men requiring a repeat biopsy. METHODS: All underwent 3 T mpMRI and transperineal template prostate mapping biopsies (TTPM biopsies). Multiparametric MRI was reported using Likert scores and radiologists were blinded to initial biopsies. Men were blinded to mpMRI results. Clinically significant prostate cancer was defined as Gleason ⩾4+3 and/or cancer core length ⩾6 mm. RESULTS: Two hundred and forty-nine had both tests with mean (s.d.) age was 62 (7) years, median (IQR) PSA 6.8 ng ml (4.98-9.50), median (IQR) number of previous biopsies 1 (1-2) and mean (s.d.) gland size 37 ml (15.5). On TTPM biopsies, 103 (41%) had clinically significant prostate cancer. Two hundred and fourteen (86%) had a positive prostate mpMRI using Likert score ⩾3; sensitivity was 97.1% (95% confidence interval (CI): 92-99), specificity 21.9% (15.5-29.5), negative predictive value (NPV) 91.4% (76.9-98.1) and positive predictive value (PPV) 46.7% (35.2-47.8). One hundred and twenty-nine (51.8%) had a positive mpMRI using Likert score ⩾4; sensitivity was 80.6% (71.6-87.7), specificity 68.5% (60.3-75.9), NPV 83.3% (75.4-89.5) and PPV 64.3% (55.4-72.6). CONCLUSIONS: In men advised to have a repeat prostate biopsy, prostate mpMRI could be used to safely avoid a repeat biopsy with high sensitivity for clinically significant cancers. However, such a strategy can miss some significant cancers and overdiagnose insignificant cancers depending on the mpMRI score threshold used to define which men should be biopsied.

Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi-institutional analysis of 418 patients.

OBJECTIVE: To report the oncological outcome of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database. PATIENTS AND METHODS: This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S-HIFU from 1995 to 2009. The biochemical failure-free survival (bFFS) rate was based on the 'Phoenix' definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer-specific death. Kaplan-Meier analysis was performed examining overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). Adverse events and quality of life status are reported. RESULTS: In all, 418 patients with a mean (SD) follow-up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S-HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S-HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre-EBRT low-, intermediate- and high-risk patients, respectively. The 5-year bFFS rate was 67%, 42% and 22% for pre-S-HIFU PSA level ≤4, 4-10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post-RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto-urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group. CONCLUSION: S-HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7-year CSS and MFS rates of >80% at a price of significant morbidity. S-HIFU should be initiated early following EBRT failure.