Histotripsy Focal Ablation of Implanted Prostate Tumor in an ACE-1 Canine Cancer Model

• Published in: The Journal of urology Vol. 188; no. 5; pp. 1957 - 1964
• Main Authors: Schade, George R, Keller, Jill, Ives, Kim, Cheng, Xu, Rosol, Thomas J, Keller, Evan, Roberts, William W
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2012; Elsevier
• Subjects: Ablation Techniques - methods; Animals; Biological and medical sciences; Disease Models, Animal; Dogs; Gynecology. Andrology. Obstetrics; Male; Male genital diseases; Medical sciences; necrosis; Neoplasm Transplantation; Nephrology. Urinary tract diseases; prostate; Prostatectomy - methods; prostatic neoplasms; Prostatic Neoplasms - pathology; Tumors; Tumors of the urinary system; ultrasonography; Urinary tract. Prostate gland; Urology; transrectal ultrasound; HIFU; prostate cancer; ultrasonography; necrosis; prostatic neoplasms; dogs; prostate; high intensity focused ultrasound; TRUS; PCa; Animal model; Prostate tumor; Nephrology; Prostate disease; Urology; Necrosis; Urogenital system; Male genital diseases; Dog; Sonography; Fissipedia; Carnivora; Urinary system disease; Implant; Malignant tumor; Ablation; Vertebrata; Mammalia; Implanted; Animal; Echography; Prostate; Cancer
• ISSN: 0022-5347; 1527-3792; 1527-3792
• DOI: 10.1016/j.juro.2012.07.006

Purpose Histotripsy is a nonthermal ablative focused ultrasound technology with possible future applications for prostate cancer focal therapy. We used the ACE-1 prostate tumor model and evaluated the feasibility of treating prostate tumors with histotripsy. Materials and Methods A total of 10 immunosuppressed (cyclosporine treated) canine subjects received transrectal ultrasound guided percutaneous intraprostatic injection of ACE-1 canine prostate cancer cells. Prostates were serially imaged with transrectal ultrasound to monitor tumor growth. Subjects were sham treated (3) or underwent transabdominal histotripsy of the prostate, which targeted implanted tumor and adjacent parenchyma using a 750 kHz piezoelectric ultrasound therapy transducer. Prostates were examined histologically to confirm tumor and the histotripsy treatment effect. Results ACE-1 tumors were visualized on transrectal ultrasound in all 10 subjects within 2 weeks of tumor injection. Lesions demonstrated growth in the prostatic capsule, glandular lobules, fibrous septa and periurethral stroma with significant desmoplastic reaction and areas of central necrosis on histology. Lymph node and/or pulmonary metastases developed in 4 subjects. Ultrasound tumor localization and initiation of cavitation during histotripsy therapy were feasible in all treated subjects. Histologically there was evidence of homogenization of tumor and prostatic parenchyma in all 4 acute subjects with necrosis and hemorrhage in the 3 chronic subjects. Conclusions This study shows the feasibility of histotripsy destruction of prostate tumors in a canine ACE-1 model. It suggests a potential role for histotripsy based focal therapy for prostate cancer. Further studies are needed to better characterize the effects of histotripsy on malignant tissues.