Faculty News
"Non-invasive Ultrasonic Prostate Tissue Ablation using Histotripsy in treatment of Prostate Cancer"
Charles Cain, PhD and Will Roberts, MD
Third year of funding- 2008 funding: $100,000; funding to date $350,000
Invasive therapies for treating cases of enlarged prostate in older men are often painful and costly. Non-invasive therapies also tend to be painful and/or ineffective, while drugs tend to be only marginally effective. A non-invasive soft tissue ablation therapy called Histotripsy has been developed by scientists at the University of Michigan under the leadership of Charles Cain, PhD. Histotripsy employs high intensity focused ultrasound that is pulsed to induce cavitation, resulting in cellular breakdown of the target tissue. Live ultrasound imaging is used to monitor the process which is very precise because it is non-thermal and is controlled in real time.
The potential for this ablation technique to treat benign prostatic hyperplasia (BPH) non-invasively and provide immediate relief of symptoms was suggested by early experiments that were part of two previous Coulter grants. The project team hypothesized that targeting the urethra and adjacent prostate tissue would result in an enlargement of the urethral channel. The debris from cavitation has been shown to be extremely fine such that disrupted tissue could be voided from the newly enlarged channel providing immediate relief of symptoms.
BPH is a common pathological finding in older men. The incidence of BPH increases from 50% of the male population at age 50 to 80% by age 80. The prostate is a reproductive organ located in the male pelvis that encircles the urethra just distal to the bladder. Prostatic enlargement often causes compression of the urethra and results in difficulty voiding urine (weak stream, straining to void, incomplete emptying, and frequent urination). To better assess the clinical impact of BPH, the American Urological Association (AUA) developed the AUA symptom score, an instrument that quantifies lower urinary tract symptoms (LUTS). Moderate to severe LUTS were found to occur on 29%, 40%, and 56% of men in their 50s, 60s, and 70s respectively. BPH induced LUTS can have a dramatic effect on quality of life and lead to more severe complications including urinary retention, recurrent urinary tract infections, bladder stones, bladder decompensation, and kidney damage.
In 1986, approximately 350,000 Medicare patients underwent transurethral resection of the prostate (TURP). In the past 10 years alternatives to TURP including pharmacologic therapy and less invasive transurethral ablative technologies have been developed. Medical therapy, designed to shrink the prostate and decrease the smooth muscle tone within the prostate to promote better urine flow, is commonly employed early in the disease for men with mild LUTS.
Although effective in some patients, 20% - 40% of patients at 12 months and 50% at 3 years had discontinued therapy either due to disease progression or the difficulties associated with a long-term commitment to expensive pharmacologic therapy. Less invasive transurethral ablative technologies (e.g. radiofrequency ablation, microwave therapy, and thermotherapy) deliver energy to the prostate to induce a coagulative necrosis of prostatic tissue. Although less morbid than TURP, less invasive modalities can only be utilized for select patients with favorable prostate anatomy. Furthermore these technologies produce a lesser degree of relief than TURP. The disappointing results achieved with currently available less invasive modalities may be secondary to the manner in which tissue is destroyed. With TURP the BPH tissue is removed leaving a cavity for improved urinary flow. With less invasive modalities the prostate tissue is thermally treated resulting in coagulative necrosis which is left in-situ and experiences variable degrees of reabsorption. As a result, TURP (a major surgical procedure) is still considered the gold standard treatment for BPH today.
It is believed that non-invasive prostate debulking can be achieved with acoustic cavitation that produces mechanical tissue ablation (histotripsy). Acoustic cavitation is a phenomenon where rapid cycling from compression to rarefaction results in formation of microbubbles within the tissue. These bubbles have been observed to oscillate and violently collapse releasing tremendous energy. The net effect of cavitation is localized stresses and pressures that can mechanically fragment and subdivide the tissue resulting in cellular destruction. Histotripsy, though non-invasive and likely less morbid than TURP, also debulks the prostate and may produce equivalent outcomes. Prostatic histotripsy may also provide a more effective alternative treatment for patients who currently are pursuing pharmacologic management or less-invasive modalities.
Posted on May 27, 2008, 10:02 am