Focal High-intensity Focused Ultrasound Research Articles

MRI-based monitoring of prostate cancer after HIFU: Inter-reader agreement and diagnostic performance of the PI-FAB score

PurposeTo investigate inter-reader agreement, and diagnostic performance of the Prostate Imaging after Focal Ablation (PI-FAB) score applied to multiparametric MRI (mpMRI) in patients who underwent focal high-intensity focused ultrasound (HIFU) therapy for localized prostate cancer. MethodsIn this retrospective, IRB-approved, single-center study, 73 men, who underwent focal HIFU treatment and received follow-up mpMRIs with subsequent prostate biopsies, were included. The PI-FAB score was applied to follow-up MRIs at 6, 12, and 36 months post-HIFU by two radiologists with different experience levels. Inter-reader agreement was assessed using Gwet’s AC1, and the diagnostic performance of the PI-FAB score was assessed in relation to histopathologic results of subsequent prostate biopsies for each reader. ResultsPI-FAB scores showed substantial to almost perfect inter-reader agreement (AC1: 0.80–0.95) and demonstrated high specificity (Reader 1: 90–98 %, Reader 2: 87–98 %) and NPVs (Reader 1: 91–100 %, Reader 2: 88–97 %) in ruling out residual or recurrent in-field prostate cancer post-HIFU. Sensitivity (Reader 1: ≥43 %, Reader 2: ≥14 %) and PPVs (Reader 1: ≥33 %, Reader 2: ≥14 %) were mostly relatively lower, with notable disparities between the two readers, indicating the potential influence of radiologist experience. ConclusionsThe PI-FAB score provides a consistent and reliable tool for post-HIFU monitoring of prostate cancer using mpMRI. It demonstrates substantial to almost perfect inter-reader agreement and is particularly effective in excluding in-field residual or recurrent prostate cancer post-HIFU treatment. Its application can potentially enhance post-treatment patient care, emphasizing its value as a non-invasive MRI-based monitoring approach after focal ablative therapy of the prostate.

High-intensity focused ultrasound with visually directed power adjustment for focal treatment of localized prostate cancer: systematic review and meta-analysis

PurposeTo characterize patient outcomes following visually directed high-intensity focused ultrasound (HIFU) for focal treatment of localized prostate cancer.MethodsWe performed a systematic review of cancer-control outcomes and complication rates among men with localized prostate cancer treated with visually directed focal HIFU. Study outcomes were calculated using a random-effects meta-analysis model.ResultsA total of 8 observational studies with 1,819 patients (median age 67 years; prostate-specific antigen 7.1 mg/ml; prostate volume 36 ml) followed over a median of 24 months were included. The mean prostate-specific antigen nadir following visually directed focal HIFU was 2.2 ng/ml (95% CI 0.9–3.5 ng/ml), achieved after a median of 6 months post-treatment. A clinically significant positive biopsy was identified in 19.8% (95% CI 12.4–28.3%) of cases. Salvage treatment rates were 16.2% (95% CI 9.7–23.8%) for focal- or whole-gland treatment, and 8.6% (95% CI 6.1–11.5%) for whole-gland treatment. Complication rates were 16.7% (95% CI 9.9–24.6%) for de novo erectile dysfunction, 6.2% (95% CI 0.0–19.0%) for urinary retention, 3.0% (95% CI 2.1–3.9%) for urinary tract infection, 1.9% (95% CI 0.1–5.3%) for urinary incontinence, and 0.1% (95% CI 0.0–1.4%) for bowel injury.ConclusionLimited evidence from eight observational studies demonstrated that visually directed HIFU for focal treatment of localized prostate cancer was associated with a relatively low risk of complications and acceptable cancer control over medium-term follow-up. Comparative, long-term safety and effectiveness results with visually directed focal HIFU are lacking.

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

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. 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. 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. 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.

Single-center, prospective phase 2 trial of high-intensity focused ultrasound (HIFU) in patients with unilateral localized prostate cancer: good functional results but oncologically not as safe as expected

PurposeFocal therapy (FT) for localized prostate cancer (PCa) is only recommended within the context of clinical trials by international guidelines. We aimed to investigate oncological follow-up and safety data of focal high-intensity focused ultrasound (HIFU) treatment.MethodsWe conducted a single-center prospective study of 29 patients with PCa treated with (focal) HIFU between 2016 and 2021. Inclusion criteria were unilateral PCa detected by mpMRI-US-fusion prostate biopsy and maximum prostate specific antigen (PSA) of 15 ng/ml. Follow-up included mpMRI-US fusion-re-biopsies 12 and 24 months after HIFU. No re-treatment of HIFU was allowed. The primary endpoint was failure-free survival (FFS), defined as freedom from intervention due to cancer progression.ResultsMedian follow-up of all patients was 23 months, median age was 67 years and median preoperative PSA was 6.8 ng/ml. One year after HIFU treatment PCa was still detected in 13/ 29 patients histologically (44.8%). Two years after HIFU another 7/29 patients (24.1%) were diagnosed with PCa. Until now, PCa recurrence was detected in 11/29 patients (37.93%) which represents an FFS rate of 62%.One patient developed local metastatic disease 2 years after focal HIFU. Adverse events (AE) were low with 70% of patients remaining with sufficient erectile function for intercourse and 97% reporting full maintenance of urinary continence.ConclusionHIFU treatment in carefully selected patients is feasible. However, HIFU was oncologically not as safe as expected because of progression rates of 37.93% and risk of progression towards metastatic disease. Thus, we stopped usage of HIFU in our department.

The Association of Tissue Change and Treatment Success During High-intensity Focused Ultrasound Focal Therapy for Prostate Cancer

BackgroundTissue preservation strategies have been increasingly used for the management of localized prostate cancer. Focal ablation using ultrasound-guided high-intensity focused ultrasound (HIFU) has demonstrated promising short and medium-term oncological outcomes. Advancements in HIFU therapy such as the introduction of tissue change monitoring (TCM) aim to further improve treatment efficacy. ObjectiveTo evaluate the association between intraoperative TCM during HIFU focal therapy for localized prostate cancer and oncological outcomes 12 mo afterward. Design, setting, and participantsSeventy consecutive men at a single institution with prostate cancer were prospectively enrolled. Men with prior treatment, metastases, or pelvic radiation were excluded to obtain a final cohort of 55 men. InterventionAll men underwent HIFU focal therapy followed by magnetic resonance (MR)-fusion biopsy 12 mo later. Tissue change was quantified intraoperatively by measuring the backscatter of ultrasound waves during ablation. Outcome measurements and statistical analysisGleason grade group (GG) ≥2 cancer on postablation biopsy was the primary outcome. Secondary outcomes included GG ≥1 cancer, Prostate Imaging Reporting and Data System (PI-RADS) scores ≥3, and evidence of tissue destruction on post-treatment magnetic resonance imaging (MRI). A Student's t - test analysis was performed to evaluate the mean TCM scores and efficacy of ablation measured by histopathology. Multivariate logistic regression was also performed to identify the odds of residual cancer for each unit increase in the TCM score. Results and limitationsA lower mean TCM score within the region of the tumor (0.70 vs 0.97, p = 0.02) was associated with the presence of persistent GG ≥2 cancer after HIFU treatment. Adjusting for initial prostate-specific antigen, PI-RADS score, Gleason GG, positive cores, and age, each incremental increase of TCM was associated with an 89% reduction in the odds (odds ratio: 0.11, confidence interval: 0.01–0.97) of having residual GG ≥2 cancer on postablation biopsy. Men with higher mean TCM scores (0.99 vs 0.72, p = 0.02) at the time of treatment were less likely to have abnormal MRI (PI-RADS ≥3) at 12 mo postoperatively. Cases with high TCM scores also had greater tissue destruction measured on MRI and fewer visible lesions on postablation MRI. ConclusionsTissue change measured using TCM values during focal HIFU of the prostate was associated with histopathology and radiological outcomes 12 mo after the procedure. Patient summaryIn this report, we looked at how well ultrasound changes of the prostate during focal high-intensity focused ultrasound (HIFU) therapy for the treatment of prostate cancer predict patient outcomes. We found that greater tissue change measured by the HIFU device was associated with less residual cancer at 1 yr. This tool should be used to ensure optimal ablation of the cancer and may improve focal therapy outcomes in the future.

Risk Factors for Severe Erectile Dysfunction after Focal Therapy with High-Intensity Focused Ultrasound for Prostate Cancer.

The present study aimed to analyze the effect of predisposing clinical factors for severe erectile dysfunction (ED) in patients treated with focal therapy using high-intensity focused ultrasound (HIFU) for localized prostate cancer (PC). Patients without severe ED (International Index of Erectile Function-5 [IIEF-5] score ≥ 8) before focal HIFU therapy were included. A total of 92 of the 240 patients met the inclusion criteria and were included. The rate of severe ED (IIEF-5 ≤ 7) was 36% 12 months after treatment. Multivariable logistic regression analysis showed that the pre-procedural lower IIEF-5 score (odds ratio [OR] 0.812, p = 0.005), the pre-procedural lower score of the sexual domain of the Expanded Prostate Cancer Index Composite (OR 0.960, p = 0.038), and the treatment of the edge of the peripheral zone (PZ) in proximity to the neurovascular bundle (NVB) [treated vs. untreated, OR 8.048, p = 0.028] were significant risk factors for severe ED at 12 months after treatment. In conclusion, pre-procedural lower erectile function and treatment of the part in proximity to the NVB were significant risk factors for severe ED after focal therapy.

Medium-term Oncological Efficacy and Patient-reported Outcomes After Focal High-intensity Focused Ultrasound: The FOXPRO Trial

BackgroundMultiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound (TRUS) fusion-guided high-intensity focused ultrasound (HIFU) is a focal treatment option for MRI-visible localized prostate cancer (PCa). High-quality evidence regarding the clinical efficacy remains limited. ObjectiveTo assess medium-term oncological efficacy along with patient-reported outcome measures (PROMs). Design, setting, and participantsThis prospective single-center cohort study was performed from 2014 to 2020. Patients with primary International Society of Urological Pathologists (ISUP) grade group (GG) ≤2 by combined MRI/TRUS fusion and systematic prostate biopsy and prostate-specific antigen (PSA) <10 ng/ml were included. InterventionMRI/TRUS fusion-guided focal HIFU therapy. Outcome measurements and statistical analysisThe primary outcome was the cancer-free rate of the HIFU-treated lesion by biopsy after 1 yr. Secondary endpoints included salvage treatment–free survival (STFS), metastasis-free survival (MFS), overall survival (OS), and PROMs according to International Consortium for Health Outcomes Measurement recommendations. Results and limitationsFifty patients were included (median [range] age 68 [48–80] yr; median PSA 6.5 [1.2–9.9] ng/ml; GG 1 54% [n = 27], and GG 2 46% [n = 23]). The median (range) PSA decrease from baseline to 12 mo was 51% (35.9–72.7%). In total, 37/50 patients (74%) underwent a 1-yr biopsy. PCa was detected in 23 patients (46%; GG 1 20% [n = 10]; GG >1 26% [n = 13]; infield 40% [n = 20]). At a median follow-up of 42 (13–73) mo, PCa was detected in 30 men (60%). Among all patients, 19 (38%) underwent salvage treatments (median [95% confidence interval] STFS 53 [44.3–61.7] mo). MFS and OS were 100% and 98%, respectively. The Expanded Prostate Cancer Index Composite-26 sexual domain decreased by 20.8 points (p = 0.372). ConclusionsMRI/TRUS-guided focal HIFU therapy results in complete cancer ablation in only half of the treated patients after 1 yr, with further recurrences at medium-term follow-up. A decline of potency occurs in a subset of patients. Patient summaryFocal image-guided high-intensity focused ultrasound therapy controls cancer in one of two patients. Its impact on urinary continence and erectile function is low.

Evaluation of post-ablation mpMRI as a predictor of residual prostate cancer after focal high intensity focused ultrasound (HIFU) ablation.

To evaluate the performance of multiparametric magnetic resonance imaging (mpMRI) and PSA testing in follow-up after high intensity focused ultrasound (HIFU) focal therapy for localized prostate cancer. A total of 73 men with localized prostate cancer were prospectively enrolled and underwent focal HIFU followed by per-protocol PSA and mpMRI with systematic plus targeted biopsies at 12 months after treatment. We evaluated the association between post-treatment mpMRI and PSA with disease persistence on the post-ablation biopsy. We also assessed post-treatment functional and oncological outcomes. Median age was 69 years (Interquartile Range (IQR): 66-74) and median PSA was 6.9 ng/dL (IQR: 5.3-9.9). Of 19 men with persistent GG ≥ 2 disease, 58% (11 men) had no visible lesions on MRI. In the 14 men with PIRADS 4 or 5 lesions, 7 (50%) had either no cancer or GG 1 cancer at biopsy. Men with false negative mpMRI findings had higher PSA density (0.16 vs. 0.07 ng/mL2, P = 0.01). No change occurred in the mean Sexual Health Inventory for Men (SHIM) survey scores (17.0 at baseline vs. 17.7 post-treatment, P = 0.75) or International Prostate Symptom Score (IPSS) (8.1 at baseline vs. 7.7 at 24 months, P = 0.81) after treatment. Persistent GG ≥ 2 cancer may occur after focal HIFU. mpMRI alone without confirmatory biopsy may be insufficient to rule out residual cancer, especially in patients with higher PSA density. Our study also validates previously published studies demonstrating preservation of urinary and sexual function after HIFU treatment.

A Review of High Intensity Focused Ultrasound Focal Therapy Results Using the MRI Ultrasound Fusion

To provide its therapeutic effects, High-Intensity Focused Ultrasound (HIFU) treatment makes use of ultrasonic waves that are transmitted through tissue medium. This non-invasive technology shows capacity for a variety of medical applications, including tumor ablation, vascular coagulation, and gene and drug delivery. Nonetheless, there are many problems that can arise from using this technology. The goal of this research was to examine the effectiveness of focused HIFU treatment for prostate cancer by employing an MRI-US fusion platform to pinpoint the precise location of the tumor and administer the therapy. Focal HIFU treatment for locally advanced prostate cancer is a prospective case series employed in this article. There must not be a Gleason 5 signal on the prostatic biopsy and the focal lesion must be less than 20 mm in size on multiparametric Magnetic Resonance Imaging (MRI) for inclusion. The first half of the series were treated with traditional HIFU focused treatment, whereas the second half were treated using an MRI-US fusion platform. Requirement for salvage treatment was used as the major outcome measure of treatment efficacy. Results of supplementary interest were Prostate Specific Antigen (PSA) change, intraoperative morbidity, postoperative clinical outcome, and tumor resurgence in follow-up biopsies.

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

BackgroundFocal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment. ObjectiveTo report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer. Design, setting, and participantsAn 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 analysisFailure-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 limitationsThe 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. ConclusionsFocal 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 summaryFocal 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.

MP46-20 HIGH-RESOLUTION, 18F-FLUCICLOVINE PET-MRI FOR MAPPING PROSTATE CANCER PRIOR TO FOCAL HIGH-INTENSITY FOCUSED ULTRASOUND

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy (MP46)1 Sep 2021MP46-20 HIGH-RESOLUTION, 18F-FLUCICLOVINE PET-MRI FOR MAPPING PROSTATE CANCER PRIOR TO FOCAL HIGH-INTENSITY FOCUSED ULTRASOUND Timothy Daskivich, Michael Luu, Jenny Park, Alessandro D'Agnolo, Rola Saouaf, Debiao Li, Yaniv Raphael, Sardius Chen, Yibin Xie, Marcio Diniz, Christopher Nguyen, and Hyung Kim Timothy DaskivichTimothy Daskivich More articles by this author , Michael LuuMichael Luu More articles by this author , Jenny ParkJenny Park More articles by this author , Alessandro D'AgnoloAlessandro D'Agnolo More articles by this author , Rola SaouafRola Saouaf More articles by this author , Debiao LiDebiao Li More articles by this author , Yaniv RaphaelYaniv Raphael More articles by this author , Sardius ChenSardius Chen More articles by this author , Yibin XieYibin Xie More articles by this author , Marcio DinizMarcio Diniz More articles by this author , Christopher NguyenChristopher Nguyen More articles by this author , and Hyung KimHyung Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002067.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial-gland high intensity focused ultrasound (HIFU) requires accurate localization of cancer within the prostate. We conducted a pilot trial to determine if a novel high-resolution DWI MRI sequence (hrMRI) and 18F-fluciclovine-PET-MRI could identify biopsy-proven cancers not seen on standard multiparametric MRI (mpMRI). METHODS: Candidates for hemigland HIFU were prospectively enrolled (unilateral Gleason≥7, PSA<20, stage≤cT2c) and underwent 18F-fluciclovine-PET-MRI, hrMRI and mpMRI. MR/ultrasound-fusion+systematic mapping biopsy was performed, targeting lesions (PIRADS3+ or PET+) identified on any imaging modality. Patients with unilateral high-grade disease underwent partial-gland HIFU. The primary endpoint was sensitivity of imaging modalities for biopsy-proven cancer. The secondary endpoint was cancer control based on 6-month-post-HIFU-MR/ultrasound-fusion biopsy. RESULTS: Of 20 men enrolled, 13 were eligible for imaging and post-HIFU analysis. 18F-fluciclovine-PET-MRI and hrMRI showed a trend toward improvement in sensitivity for detection of any cancer over mpMRI alone. When a positive test was defined as lesions that were either hrMRI (PIRADS 3-5) or PET positive, sensitivity for detection of any cancer was 0.56 (95%CI,0.44–0.78) compared with 0.41 (95%CI, 0.31–0.60) with mpMRI alone (p=0.056). For GG2+ cancers, sensitivity was 0.60 (95%CI, 0.46–0.90) compared with 0.55 (95%CI, 0.42–0.83) with mpMRI alone (p=0.32). Five PIRADS3+ lesions were identified on hrMRI but not mpM RI, of which 2 were biopsy-proven GG1 cancers. Eleven lesions were identified on PET but not mpMRI, of which 1 was biopsy-proven GG2 cancer, which affected the HIFU treatment template (Figure). One of eleven subjects had residual GG2 disease on 6-month post-HIFU biopsy. CONCLUSIONS: High-resolution PET MRI may help to fully characterize tumor burden for mapping prior to hemigland or focal HIFU. Source of Funding: Institutional © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e821-e822 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Timothy Daskivich More articles by this author Michael Luu More articles by this author Jenny Park More articles by this author Alessandro D'Agnolo More articles by this author Rola Saouaf More articles by this author Debiao Li More articles by this author Yaniv Raphael More articles by this author Sardius Chen More articles by this author Yibin Xie More articles by this author Marcio Diniz More articles by this author Christopher Nguyen More articles by this author Hyung Kim More articles by this author Expand All Advertisement Loading ...

Focal High-Intensity Focused Ultrasound Ablation of the Prostate.

With the advancement of early detection tools for prostate cancer and ability to better localize disease, there has been increased interest in focal or targeted therapies that carry less morbidity than traditional whole-gland treatments. The Sonablate® high-intensity focused ultrasound (HIFU) device has Food and Drug Administration (FDA) 510(K) clearance in the United States for ablation of prostate tissue. HIFU utilizes an ultrasound (US) transducer that focuses US beams on a preset point as much as 4 cm from the energy source without injuring intervening tissue. The Sonablate system guides the surgeon step-by-step to perform effective ablation of a target lesion. The surgeon can assess treatment effect with tissue change monitoring, and care is taken to prevent rectal wall injury. We believe hemiablation is the most favorable focal HIFU treatment to optimize cancer control and minimize the side effects associated with whole gland therapy. We recommend considering HIFU ablation as an extension of active surveillance rather than definitive treatment. Further research on long-term oncologic and functional outcomes is warranted.

Salvage Robotic-assisted Laparoscopic Radical Prostatectomy Following Focal High-Intensity Focused Ultrasound for ISUP 2/3 Cancer

ObjectiveTo report feasibility and outcome of salvage robotic-assisted laparoscopic radical prostatectomy (S-RALP) after focal therapy using high-intensity focused ultrasound (HIFU) treatment compared to primary robotic-assisted laparoscopic radical prostatectomy (pRALP). MethodsIn this bicentric trial patients undergoing S-RALP for detection of WHO2016/ISUP Grade Group 2 or 3 prostate cancer were previously treated in prospective focal HIFU trials. Perioperative data, complications, oncological and functional outcome were analysed. Patients who underwent pRALP were matched in a ratio 2(pRALP):1(S-RALP) according to preoperatively functional, oncological and clinical parameters. ResultsA total of 39 patients were included in the study (13S-RALP, 26pRALP). Median operative time in the S-RALP group was 260minutes (pRALP: 257minutes), blood loss was 230ml (pRALP: 300ml). Complications occurred in 46.2% (6/13) of S-RALP patients (pRALP: 26.9%), including four Clavien-Dindo III complications (pRALP: 2/26). In S-RALP adverse histological outcome (≥pT3a, pN+ or R1) was detected in 23.1% (3/13) (pRALP: 26.9%). There was one patient with PSA-persistence (pRALP: 2/26). Regarding functional outcomes there was no difference between the two groups observed (incontinence P=.71, erectile function P=.21). ConclusionS-RALP should be offered to patients with an early relapse after focal HIFU. The early oncological outcome is satisfactory and functional outcome one year postoperatively is similar to pRALP. However, S-RALP is associated with a higher rate of Clavien-Dindo III complications (mainly, placement of a drainage), of which patients should be informed beforehand.

The utility of intraoperative contrast-enhanced ultrasound in detecting residual disease after focal HIFU for localized prostate cancer

Background and objectivesFocal high intensity focused ultrasound (HIFU) is an emerging treatment for selected men with localized prostate cancer. A limitation of HIFU is the absence of a reliable tool to measure treatment effect intraoperatively. Contrast-enhanced ultrasound (CEUS) has been shown to be a promising modality for assessing the extent and boundaries of tissue ablation. The aim of this study was to assess the value of CEUS immediately after focal HIFU. Materials and methodsRetrospective analysis of a prospectively maintained registry including consecutive men undergoing focal HIFU (Focal One). Candidates for focal HIFU were treatment naive men with ≥10 years life expectancy, prostate-specific antigen (PSA) ≤ 20 ng/ml, TNM primary tumor, regional lymph nodes, distant metastasis stage ≤ T2c N0 M0 with a multiparametric MRI (mpMRI) visible lesion concordant with histologically proven prostate cancer. CEUS evaluation was performed immediately at the end of the procedure. Based on the surgeon's estimation of CEUS imaging, re-HIFU was performed, followed by another CEUS evaluation. To test our hypothesis, the results of the CEUS were compared to the results of early mpMRI to rule out clinically significant cancer. The concordance between the 2 tests was measured using the Cohen's kappa. The best model including relevant predictors was calculated with CEUS or with mpMRI to determine their respective added value. ResultsOf 66 men who underwent HIFU, 32 met eligibility criteria. Bifocal treatment was performed in 1 man, increasing the number of treated lesions to 33. Further ablation based on CEUS was delivered intraoperatively to 13 lesions (39%). The positive biopsy rate for clinically significant cancer in the treated zones was 30% (10/33). The negative predictive value of CEUS and early mpMRI was 71% (95% confidence interval: 59%–82%). Concordance between CEUS and mpMRI was significant with a 72.7% agreement (P = 0.001). The model with CEUS showed the best accuracy with an area under the curve of 0.881. ConclusionCEUS has a higher added value compared to early mpMRI in ruling out clinically significant cancer after focal HIFU. It should be evaluated whether the use of CEUS intraoperatively enhances the efficacy of focal HIFU.

An Exploratory Study of Dose Escalation vs Standard Focal High-Intensity Focused Ultrasound for Treating Nonmetastatic Prostate Cancer.

Objective: Analysis of treatment success regarding oncological recurrence rate between standard and dose escalation focal high-intensity focused ultrasound (HIFU) of prostate cancer. Materials and Methods: In this analysis of our prospectively maintained HIFU (Sonablate® 500) database, 598 patients were identified who underwent a focal HIFU (Sonablate 500) between March 2007 and November 2016. Follow-up occurred with 3-monthly clinic visits and prostate specific antigen (PSA) testing in the first year. Thereafter, PSA was measured 6-monthly or annually at least. Routine and for-cause multiparametric MRI (mpMRI) was conducted with biopsy for MRI suspicion of recurrence. Treatments were delivered in a quadrant or hemiablation fashion depending on the gland volume as well as tumor volume and location. Before mid-2015, standard focal HIFU was used (two HIFU blocks); after this date, some urologists conducted dose escalation focal HIFU (three overlapping HIFU blocks). Propensity matching was used to ensure two matched groups, leading to 162 cases for this analysis. Treatment failure was defined by any secondary treatment (systemic therapy, cryotherapy, radiotherapy, prostatectomy, or further HIFU), metastasis from prostate cancer without further treatment, tumor recurrence with Gleason score ≥7 (≥3 + 4) on prostate biopsy without further treatment, or prostate cancer-related mortality. Complications and side-effects were also compared. Results: Median age was 64.5 years (interquartile range [IQR] 60-73.5) in the standard focal-HIFU group and 64.5 years (IQR 60-69) in the dose-escalation group. Median prostate volume was 37 mL (IQR 17-103) in the standard group and 47.5 mL (IQR 19-121) in the dose-escalation group. As tumor volume on mpMRI and Gleason score were major matching criteria, these were identical with 0.43 mL (IQR 0.05-2.5) and Gleason 3 + 3 = 6 in 1 out of 32 (3%), 3 + 4 = 7 in 27 out of 32 (84%), and 4 + 3 = 7 in 4 out of 32 (13%). Recurrence in treated areas was found in 10 out of 32 (31%) when standard treatment zones were applied, and in 6 out of 32 (19%) of dose-escalation focal HIFU (p = 0.007). Conclusion: This exploratory study shows that dose escalation focal HIFU may achieve higher rates of disease control compared with standard focal HIFU. Further prospective comparative studies are needed.

V14-06 CETRUS; CONTRAST-ENHANCED TRANS-RECTAL ULTRASOUND TO MONITOR POST-TREATMENT RECURRENCE AFTER FOCAL HIFU OF PROSTATE

You have accessJournal of UrologyProstate Cancer (V14)1 Apr 2020V14-06 CETRUS; CONTRAST-ENHANCED TRANS-RECTAL ULTRASOUND TO MONITOR POST-TREATMENT RECURRENCE AFTER FOCAL HIFU OF PROSTATE Aliasger Shakir*, Atsuko Fujihara, Tsuyoshi Iwata, Alessandro Tafuri, Cacciamani Giovanni, Suzanne Palmer, Inderbir Gill, and Andre Luis Abreu Aliasger Shakir*Aliasger Shakir* More articles by this author , Atsuko FujiharaAtsuko Fujihara More articles by this author , Tsuyoshi IwataTsuyoshi Iwata More articles by this author , Alessandro TafuriAlessandro Tafuri More articles by this author , Cacciamani GiovanniCacciamani Giovanni More articles by this author , Suzanne PalmerSuzanne Palmer More articles by this author , Inderbir GillInderbir Gill More articles by this author , and Andre Luis AbreuAndre Luis Abreu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000982.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To assess the role of contrast enhanced trans-rectal ultrasound (CeTRUS) in the follow-up evaluation of patients who underwent focal High Intensity Focused Ultrasound (HIFU) for prostate cancer (PCa). METHODS: From our IRB-approved database (HS-17-00749), we identified 22 patients who underwent focal hemi-gland HIFU ablation of the prostate and had follow-up CeTRUS, mutiparametric MRI (mpMRI) and prostate biopsy (PBx) between 6 months to 1 year after HIFU. Salvage or whole-gland HIFU patients were excluded. CeTRUS was performed following a 2.5cc intravenous bolus of ultrasound contrast agent (LUMASON). Two-minute cine images of the regions of interest were recorded. CeTRUS findings were compared with mpMRI and the results of PBx. CeTRUS images were evaluated qualitatively. A PIRADS v2 score of 3 or higher was considered positive. Clinically significant PCa (csPCa) is defined as ISUP Grade Group (GG) ≥ 2 and non-csPCa is defined as ISUP Grade Group (GG) < 2. RESULTS: At baseline, median age and PSA was 65 year old and 5.1ng/ml. Six (26%) patients had low-risk, 13 (57%) had intermediate-risk and 3 (13%) had high-risk PCa. Post HIFU, median PSA nadir, and reduction in PSA were 1.0 ng/mL and 72%, respectively. On follow-up PBx with a median follow of 16M, 12 (55%) patients had cancer, 6 (27%) patients had csPCa, 3 (14%) patients had in-field recurrences, 9 (40%) patients had out-field recurrences, and 10 (45%) patients had a negative biopsy. Among them, three (14%) patients had in-field csPCa, 3 (14%) had out-field csPCa, 0 (0%) had in-field ncsPCa, and 6 (27%) had out-field ncsPCa. In the 3 patients with in-field csPCa (Table), MRI detected 2 (66%) lesions and CeTRUS detected 2 (66%) lesions. However, the patients with lesions detected by MRI and CeTRUS were not the same. One patient had a lesion detected by both MRI and CeTRUS, one patient had a lesion detected by MRI only and one patient had a lesion detected by CeTRUS only. Overall, among the 3 patients with in-field csPCa, 3 (100%) had lesions detected by either imaging modality. CONCLUSIONS: CeTRUS enhancement pattern showed high correlation with in-field csPCa on follow up PBx. CeTRUS and MRI were able to identify more csPCa compared to MRI alone. The addition of CeTRUS to MRI can be helpful in the follow up after focal HIFU and aid detection, and localization of csPCa. Source of Funding: This study was funded in part by the R01 grant CA205058-01 from the National Institutes of Health/ National Cancer Institute (M.C.S, I.S.G. and A.L.A.). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1307-e1308 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aliasger Shakir* More articles by this author Atsuko Fujihara More articles by this author Tsuyoshi Iwata More articles by this author Alessandro Tafuri More articles by this author Cacciamani Giovanni More articles by this author Suzanne Palmer More articles by this author Inderbir Gill More articles by this author Andre Luis Abreu More articles by this author Expand All Advertisement PDF downloadLoading ...

Follow-up after focal therapy of the prostate with high intensity focused ultrasound (HIFU) using contrast enhanced ultrasound (CEUS) in combination with MRI image fusion.

Focal therapy (FT) of the prostate for low risk prostate cancer (PCa) is an alternative to traditional definite treatment options like external beam radiotherapy or radical prostatectomy. However, follow up after FT is still challenging and is subject to current studies. Significance of imaging after FT such as multiparametric MRI (mpMRI) is currently not well established. In this study, we aimed to evaluate the efficacy of alternative imaging during the follow up of low risk PCa treated with focal HIFU therapy using CEUS and image fusion. Retrospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer treated with HIFU at our institution between October 2016 and January 2018. CEUS in combination with image fusion using an axial T2-weighted MRI sequence was performed during follow up 3, 6, 9 and 12 months after the therapy. 4 consecutive patients with Gleason score (GS) 6 and 4 patients with GS 7a prostate cancer were included in the study. Hemiablation was performed in 7 patients with unilateral tumor. One patient underwent whole gland treatment due to histological proven bilateral PCa. Mean patient age at time of therapy was 70.3 (54-83) years and mean Prostate-specific antigen (PSA) level prior treatment was 7.8 ng/ml (2.1-14.4), after 3 months mean PSA level was 3.9 ng/ml (0.1-7.2), after 6 months 3.5 ng/ml (0.2-6.0), after 9 months 3.1 ng/ml (0.2-6.8) and 3.3 ng/ml (0.2-6.1) after 12 months. CEUS showed no signs of microvascularisation after 3, 6, 9 and 12 months in the ablated zone. 3 months posttreatment the necrotic tissue was still visible in the B-mode scan, although with no signs of vascularization performing CEUS. After 6 months the ablated side of the prostate was almost completely atrophic. And after 9 months the necrotic tissue was completely resolved. Between 9 and 12 months no changes in microvascularisation and perfusion could be shown. MpMRI/CEUS image fusion is a cost-effective and feasible technique to monitor the perfusion of the ablation zone after focal therapy of the prostate.

Oncological Outcome and Value of Postoperative Magnetic Resonance Imaging after Focal High-Intensity Focused Ultrasound Therapy for Prostate Cancer

Introduction: Focal therapy (FT) by high-intensity focused ultrasound (HIFU) is an emerging option for localized prostate cancer (PC). Due to the lack of long-term data, a close monitoring after FT is essential, but there are still uncertainties about the optimal follow-up regimen. Here we report on a series of FT-HIFU patients with the focus on oncological short-term outcome and the value of postoperative magnetic resonance imaging (MRI). Methods: We included 21 patients treated by FT-HIFU using the Focal One® device (EDAP TMS, France) between November 2015 and May 2018. PC localization was assessed by preoperative multiparametric MRI (mpMRI) and transrectal ultrasound-guided targeted and systematic biopsy. Oncological follow-up included prostate-specific antigen (PSA) development, mpMRI, control biopsies (targeted and systematic) of the treated and untreated areas and salvage treatment rate. Control mpMRI and control biopsy were performed after 6–12 months. Results: 15 patients (71.4%) were managed by focal ablation of a solitary lesion, while 6 patients (28.6%) underwent zonal tumor ablation. All patients underwent control mpMRI and biopsy. After a mean follow-up period of 11.7 months, cancer relapse was detected in 8 patients (38.1%), with 4 patients (19%) having infield recurrence. Postoperative mpMRI revealed 3 out of 4 infield PC relapses but missed 5 out of 7 outfield relapses. Clinically significant cancer recurrence was present in 1 patient (4.8%), which was missed by mpMRI. Posttreatment mpMRI had a sensitivity, specificity, positive and negative predictive value of 62.5, 92.3, 83.3 and 80.0%, respectively, for overall relapse detection based on patient level. Only 1 of the 8 recurrences was suspected based on PSA progression. 4 of the 8 patients with PC relapse (19%) underwent salvage therapy (2 patients by radical prostatectomy, 2 patients by salvage FT-HIFU). Conclusion: Postoperative mpMRI might play a valuable role during follow-up after focal HIFU therapy, particularly in terms of infield relapse detection. Irrespective of mpMRI results, the repeat biopsy regimen should incorporate systematic biopsy including cores of the treated and untreated prostate areas.

Focal High-intensity Focussed Ultrasound Partial Gland Ablation for the Treatment of Localised Prostate Cancer: A Report of Medium-term Outcomes From a Single-center in the United Kingdom

To report our intermediate outcomes of the use of focal ablation for treating significant unilateral prostate cancer. This technique was adopted in our center 10 years ago. With improving diagnostic accuracy of index prostate cancer lesions and a low side-effect profile, use of focal high intensity focused ultrasound (HIFU) ablation is increasing. Patients were diagnosed using prostate specific antigen (PSA), multiparametric magnetic resonance imaging, and template transperineal biopsies. Focal ablation of significant cancer was performed with the Sonablate device. Follow-up consisted of magnetic resonance imaging scanning, PSA, validated questionnaires, biopsy for cause, and redo HIFU if required as part of the treatment strategy. A total of 107 men underwent focal HIFU. In total, 88% had intermediate/high risk disease, and the mean pre-HIFU PSA was 7.7. A total of 31% had high volume Gleason 6 disease, 55% had Gleason 3+4 disease, and 13% had Gleason ≥ 4+3 disease. In total, 54 men received a hemiablation, 10 a focal ablation, and 43 a quadrant ablation. Median follow-up was 30 months, subjects' PSA dropped to an average 71% nadir. A total of 8% had biochemical recurrence and 11% required adjuvant treatment. Freedom from additional procedures for clinically significant recurrent disease, including redo-HIFU, was 85.5%. Postoperative complications included 1% new use of pads, 1.9% urethral stricture, 2.8% post-HIFU TURP, and new onset ED of 14%. In a carefully chosen cohort of patients for focal HIFU our results suggest acceptable oncological control with minimal postoperative morbidity. Further studies are required to establish this technique as a less morbid alternative to radical therapy.

Comprehensive Evaluation of Focal Therapy Complications in Prostate Cancer: A Standardized Methodology.

Purpose: Today, up to one-third of newly diagnosed prostate cancer (PCa) cases may be suitable for focal treatment. The lack of data about the toxicity profiles of lesion-targeting therapies, however, has made it difficult to compare treatment modalities. The aim of the present study was to evaluate comprehensively the incidence, severity, and timing of onset of complications for PCa patients undergoing focal high-intensity focused ultrasound (HIFU) and focal cryosurgical ablation of the prostate (CSAP). Materials and Methods: A total of 336 patients were included who underwent focal HIFU or focal CSAP as a primary treatment for PCa between January 2009 and December 2017. Mean follow-up was 11 months (standard deviation: 3.0). All complications were captured and graded according to severity, and classified by timing of onset. Univariate and multivariate analysis was performed to identify predictors of the most common side effects. Results: There were 98 complications in 79/210 patients (38%) undergoing focal HIFU and 34 complications in 27/126 patients (21%) undergoing focal CSAP. In terms of severity, 95% of the complications of focal HIFU and 91% of the complications of focal CSAP were minor. Most complications presented in the early postoperative period. On multivariate analysis, subtotal HIFU was associated with acute urinary retention (AUR), while a smaller prostate size and longer catheterization time with dysuria. In CSAP patients, longer catheterization time was associated with AUR and urethral sloughing. The main limitation is the nonrandomized and retrospective nature. Conclusions: Focal HIFU and focal CSAP provide a tolerable toxicity, with primarily minor complications presenting in the early postoperative period.