Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer

Open AccessJournal of UrologyAdult Urology1 Mar 2021Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation Prostate CancerThis article is commented on by the following:Editorial CommentEditorial Comment Laurence Klotz, Christian P. Pavlovich, Joseph Chin, Gencay Hatiboglu, Michael Koch, David Penson, Steven Raman, Aytekin Oto, Jurgen Fütterer, Marc Serrallach, James Relle, Yair Lotan, Axel Heidenreich, Bonekamp, Masoom Haider, Temel Tirkes, Sandeep Arora, Katarzyna J. Macura, Daniel N. Costa, Thorsten Persigehl, Allan Pantuck, Joyce Bomers, Mathieu Burtnyk, Robert Staruch, and Scott Eggener KlotzLaurence Klotz *Correspondence: Division Urology, Sunnybrook Health Sciences Centre, 2075 Bayview Ave. #MG408, Toronto, Ontario M4N 3M5 telephone: 416-480-4673; FAX: 416-480-6121; E-mail Address: [email protected] Centre , University Toronto More articles this author PavlovichChristian Pavlovich Johns Hopkins ChinJoseph Chin Western HatibogluGencay Hatiboglu Hospital Heidelberg, German Cancer Research Center KochMichael Koch Indiana PensonDavid Penson Vanderbilt Medical RamanSteven Raman UCLA OtoAytekin Oto Chicago FüttererJurgen Fütterer Radboud SerrallachMarc Serrallach ResoFus Alomar (Hospital Universitari De Bellvitge) RelleJames Relle Beaumont System LotanYair Lotan UT Southwestern HeidenreichAxel Heidenreich Cologne BonekampDavid Bonekamp HaiderMasoom Haider Joint Dept Imaging, Sinai System, Institute, Lunenfeld Tanenbaum Institute Canada TirkesTemel Tirkes AroraSandeep Arora MacuraKatarzyna Macura CostaDaniel Costa PersigehlThorsten Persigehl PantuckAllan Pantuck BomersJoyce Bomers BurtnykMathieu Burtnyk Profound Financial and/or other relationship with Corp. StaruchRobert Staruch EggenerScott View All Author Informationhttps://doi.org/10.1097/JU.0000000000001362AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal under magnetic imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). Materials Methods: A total 115 men favorable intermediate risk prostate cancer across 13 centers were treated whole gland sparing urethra apical sphincter. The co-primary endpoints safety efficacy. Results: In all, 72 (63%) had grade group 2 77 (67%) NCCN® disease. Median treatment delivery time was 51 minutes 98% (IQR 95–99) coverage target volume spatial precision ±1.4 mm thermometry. Grade 3 adverse events occurred in 9 (8%) men. primary endpoint (U.S. Food Drug Administration mandated) specific antigen reduction ≥75% achieved 110 (96%) median 95% nadir 0.34 ng/ml. decreased 37 cc. Among 68 pretreatment disease, 52 (79%) free disease biopsy. Of 111 biopsy data, (65%) no evidence cancer. Erections (International Index Erectile Function question score or greater) maintained/regained 69 92 (75%). Multivariate predictors persistent at 12 months included intraprostatic calcifications screening, suboptimal PI-RADS™ greater lesion (p <0.05). Conclusions: TACT study localized demonstrated effective tissue low rates toxicity residual Abbreviations Acronyms ED erectile dysfunction GG IIEF-15 International IPSS Symptom Score MID minimally important difference MRI PSA TULSA-PRO Clinical Trial TULSA Men early stage are faced choice between active surveillance radical therapy (surgery radiation). Emerging image-guided invasive ablative treatments offer an appealing alternative potential benefits relatively nonmorbid intervention eradication. Multiparametric directs targeted enables real-time mapping temperature during MRI-guided novel procedure using TULSA-PRO® device, which leverages localization ablate via ultrasound.1–8 differs transrectal high intensity focused use continuous sweeping beam delivered (rather than discrete spots transrectally), planning thermometry, cooling rectum. Treat-and-resect studies confirmed feasibility thermally ablating accuracy 1 mm. Heating 55C 100% cell kill zone.8,9 phase I predominately acceptable profile quality life months10 but intentionally left 10% peripheral untreated. described here evaluates efficacy capsule. Methods Patients prospective, multi-center, single-arm pivotal patients (NCT02766543). protocol designed conjunction U.S. towards 510(k) clearance as device received IRB approval U.S.A., Europe Canada. Informed consent obtained all participants. Inclusion criteria age 45 80 years old, Gleason Group cancer, clinical T2b less, 15 ng/ml minimum 10-core biopsy, previous could undergo MRI. Exclusion 90 cc, width 6 cm length 5 cm; nonMRI compatible implants, infection, suspected tumor within plane MRI, cysts cm. Procedure Whole margin sphincter performed 3T (Skyra/Prisma, Siemens, Germany; Achieva/Ingenia, Philips, Netherlands). consists rigid applicator incorporates linear array 10 transducers that emit (focused blade) energy into (fig. 1). This results region Water pumped through endorectal provides peri-urethral rectal preservation.10 secured robot remote rotational motion urethra. console includes software outline boundary, monitors implements feedback. Figure 1. procedure. A, rendering device. B, sagittal coronal views 3D T2-weighted image planned zone. C, zone prescribed intraoperative axial images apex base. D, map depicting maximum temperatures treatment. E, enhancement defect confirms extent posttreatment contrast enhanced T1 weighted images. outpatient collaboration urologist radiologist previously described.8–10 Prophylactic antibiotics administered before several days after General anesthesia, cystoscopy suprapubic catheter placement outside suite. Treatment acquired used register location, guide adjustments define area. context study, plans set small avoid incontinence. During treatment, displayed every seconds determine amount each transducer. frequency, applied power rotation automatically modulated achieve target. Patient Assessment Endpoints Primary objectives frequency severity events, documented visit according Common Terminology Criteria Adverse Events. proportion achieving baseline, defined meet regulatory requirements rather oncological control. Secondary were: reduced assessed central radiology, patient reported changes quality-of-life, evaluation post multiparametric Urinary symptoms based Score11 item. MIDs voiding storage subscores half standard deviation baseline values.12 Voiding function number postvoid less 100 ml, peak urinary flow rate ml/sec greater. questionnaire 4.13 Potency evaluated 2, similar analyses focal trials.14 Other domains, daily pad urine leakage EPIC-50 questionnaire.15 Missing IPSS, IIEF, EPIC ECOG scores not interpolated. Statistical predefined 75% more baseline. With success threshold 50% patients, 1-sided exact test (α=0.025) expected reach 80% patients. For accurate estimation secondary account dropout, targeted. Continuous variables describing PSA, summarized interquartile range compared paired 2-sided Wilcoxon signed rank tests Friedman significance p <0.05. Dichotomous who experienced gain loss function, moderate change times proportions tests. logistic regression relative odds having GG2 adjusting characteristics, day parameters Analyses R (R Foundation Computing, Austria). Results men, 65 59–69) years, 6.3 (4.6–7.9) ng/ml; 38 (33%) NCCN respectively (table Seventy-two ≥GG2 (3 GG3 granted deviations due only slightly pattern 4 otherwise characteristics), 26 (23%) GG1 cores core) 17 (15%) GG1. Table Baseline demographics characteristics (IQR, range) 65.0 (59–69, 46–79) body mass index, kg/m2 27.7 (24–30, 20–43) No. race (%): White/Caucasian 99 (86) Hispanic (8) Black (4) Asian (2) Low (2 fewer any (15) High (23) (60) (3) positive 33 (29) 36 (31) 46 (40) laterality Unilateral 28 (24) Bilateral (13) contralateral 18 (16) (4.6–7.9, 0.9–17.1) T1c 89 (77) T2a 20 (17) (1) T2, unspecified substage (%):* Less cc (minimum cc) 40 (44) 60 48 (42) 7 (6) (maximum 125 21 (18) (52) No 101 (88) Yes (max mm) 14 (12) Assessed site positioning anesthetized recovery 243 201–281) minutes. 39–66, 21–112) 31–51) heated (thermal dose 240 equivalent 43C)16 accuracy/ablation 0.1±1.4 measured discharged same (55%) admitted overnight (45%), per physician’s discretion. successful removal 11–24) days. Safety (severe) including genitourinary infection (4%), urethral stricture (2%), retention (1.7%), calculus pain (1%) urinoma (1%), resolved 2). There injuries, severe incontinence requiring surgical unresponsive medication. 2. Events attributable occurring (and participants experiencing those events), subset ongoing visit. Attributable Any Occurrence Ongoing Months Description 16 (14) – 27 Hematuria 43 (35) Pain/discomfort (pelvic/genital/treatment area) 8 (7) urgency 24 Edema 25 Dysuria (11) 11 Ejaculation disorder (10) (5) Bladder spasm Urethral bleeding discharge (9) Weak stream Nondescriptive lower tract (bladder/urinary tract) Debris Urinoma infections (25) Epididymitis gastrointestinal pain/discomfort (abdominal/anorectal) (%) general (hip/back) deep vein thrombosis 3% serious (requiring hospital stay) (grade 3) listed, worst patient. events. Includes (6%) months: (1%). At months, (Grade managed oral medication new vacuum pump penile injections), (2.6%) use). majority (mild moderate) (25% asymptomatic culture 1-month analysis) antibiotics, (1.8%) recurrent months. (9%) catheterization. Moderate abdominal discomfort (3.5%) ibuprofen/acetaminophen first month. Efficacy 91–98) 0.12–0.56) (IQR) 0.5 (0.3–1.2) stable biochemical failure (PSA + ng/ml) (2.6%; table 3). Two missing values, interpolated 6-month 3. Outcomes (Median month Decline × (% year) Improvement Loss yr) Gain outcomes: PSA,* (0.2–0.9) (0.2–1.0) volume,†, ‡ (27–48) 2.8 (1.7–4.7) lesion,† 84/114 (74) 31/104 (30) questionnaires (IQR): (3–10) (7–21) (4–12) (2–12) (3–9) 8/112 7/112 Quality Life (0–3) (1–5) (1–3) (0–2) 15/113 21/113 (19) Sub-score (0–6) (2–10) (0–5) 1.9 20/113 Storage (2–6) (4–11) (3–7) (2–7) (2–5) 1.4 19/112 16/112 Domain (17–29) (2–8) (3–21) (4–24) (5–26) 38/109 6/109 Incontinence (92–100) 84 (54–100) (65–100) (79–100) (86–100) Irritative/Obstructive 93 (86–97) 54 (32–75) 86 (75–96) (82–100) 9/110 6/110 Bowel 96 (93–100) 95 (88–98) 98 97 2/110 Sexual 67 (52–75) (10–39) 31 (17–50) (18–58) 44 (19–63) 35/108 (32) 1/108 Functional flow§ (QMax), ml/s (12–22) 7/37 7/25 (28) Postvoid residual,‖ ml 30 (9–67) (0–50) 6/78 11/15 (73) Performance Status¶ men) 112/114 (98) 95/110 90/94 (96) 104/107 (97) 105/107 2/112 2/2 (100) Bolded values have statistically significant SD Nadir (0.1–0.6); (91–98); 75%: 110/115 (96%). radiology laboratory. Reduction 91% (87–96). Uroflowmetry if voided 150 more, reference more. Ref. ml. decrease perfused 91%, 27–48) 1.7–4.7) (97%) underwent 2), remaining refused. 10–12) sampled diminished volume, increased sampling density 3.5 2.1–5.7) 0.4 0.3–0.5) (14%) Similarly, (77%) either (fewer Overall, histological improvement (eradication GG2, shift GG1, eradication disease) 7% subgroups. Histological stratified 79% benefit upon systematic their tissue. Likewise, 77% 65% On multivariable analysis (supplementary table, https://www.jurology.com), presence screening (OR 11.4, CI 1.8–73, p=0.01), 96% 4.34, 1.1–18, p=0.04) PI-RADS version 8.79, 1.8–44, p=0.008). grade, bilaterality, findings, associated model did significantly addition pre-treatment Based assessment, (7%) sought additional while (10%) thus far refused further therapy. Repeat permitted protocol, opted prostatectomy radiation (4), detailed currently available. measures (IIEF-15) overall sexual satisfaction (EPIC-50 domain score) indicated initial decline followed gradual recovery, third moderately potent (IIEF-15 indicating erection firmness sufficient penetration least some time), (75%) maintained regained potency outcomes. Erection (IIEF among adequate continence normalized questions 5, respectively. declined recovered 1% incontinent (more pad/day item 5), wore 4% symptom score, voiding/storage unchanged numbers improvements declines symptoms. irritative/obstructive recovered, nearly improvement. bowel performance status 3-month Discussion large, met its morbidity. extensive markedly also functional decline. injury, returned erections penetration. met, regulators assess study. population allowed oncologically relevant stability, salvage Notwithstanding limitations comparisons extirpative therapies, 20% clinically (two-thirds bilateral cores) line accepted treatments17,18 goals retreatment therapies.19 inclusion reflects guidelines designed. However, these enrolled suspicious lesions cores. degree maintenance life.