Prostate cancer is the leading cancer diagnosis and the second leading cause of death in men, affecting one of every six men in the United States. Radiation therapy or surgery are considered the gold standard of treatment modalities for prostate cancer for organ confined disease with generally excellent outcomes, but can result in incontinence, impotence, rectal bleeding and urethral burning. Procedure costs, complete procedure duration, and therapy delivery duration remain issues. Recent advances in multi-parametric MRI and registered biopsy techniques can identify regions of dominant intraprostatic lesions (DIL) to stage and target tumors. In consideration of an alternative to ionizing radiation or prostatectomy and their associated morbidity, recent clinical studies have demonstrated the potential role of thermal ablative techniques. Although promising, these interventional technologies have limited control of the shape and extent of the ablation zone, require multiple or overlapping insertions, often with unnecessary complications. Image-guided HIFU produces multiple small ablation zones and require repositioning of focus to increase volume, but targeting regions immediately adjacent to the rectum or in the anterior prostate is difficult, MRI guided systems require complex and costly infrastructure, and long treatment durations. Intervening normal tissues, gas, and bone are problematic. There are inherent characteristics of currently applied ablation systems that (i) limit their ability to deliver truly conformal destruction of focal disease while minimizing damage to the rectum or neurovascular bundle (NVB), (ii) require significantly long procedure times, and/or (iii) are complex, at limited number of centers, and require expensive infrastructure. Proposed minimally invasive interstitial needle high-intensity ultrasound applicators with highly conformal and penetrating heating patterns, coupled with 3D tracked ultrasound image guidance, treatment planning, intraprocedure therapy monitoring, can be combined to provide an ideal mechanism for conformable precise thermal surgery in prostate. The objective of this project is development of an image- guided interstitial ultrasound ablation system combined with MP-MRI to US image registration, electromagnetic tracking, and biopsy maps for truly 3D controllable and conformal thermal ablation for treatment of both early stage localized and identified high-risk prostate cancer, which is faster and more practical than existing technologies. Unlike HIFU, our device is placed directly into the target under image guidance to treat disease focally without affecting other tissues, with a much shorter 510(k) FDA clearance path. Our approach and technology will provide sophisticated, highly-integrated 3D conformal therapy which is readily disseminated and is practical for mainstream acute care hospitals and outpatient surgery centers. We propose to develop a short duration treatment, precisely targeted therapy for prostate cancer with less side effects than radiation or surgery. The major goal of the proposed project is to complete an ultrasound image guided ultrasound ablation system to treat prostate cancer and performance validation in FDA GLP study.
? Relevance Statement About 1 man in 6 will be diagnosed with prostate cancer during his lifetime, making it the most common cancer affecting men and second in the overall population, accounting for about 33% of incident cancer cases in men. While Prostate-Specific Antigen (PSA) tests and improved imaging for early detection are continually advancing, the majority of therapies available are radical. These include surgery (open and robotic), external beam radiation therapy, and brachytherapy. More recently, ablation of the entire prostate gland with cryotherapy (freezing) or high intensity focused ultrasound has been used. Despite advances in the effectiveness of these therapies, precise targeting of the ablator device and real time monitoring and control of the zone of necrosis remain unsolved problems. Recent studies have demonstrated significant advantages of interstitial ultrasound ablators, most notably the capability to create and control treatment energy distributions (i.e. size and shape treatment zone) for conformable treatments and preserving critical non-targeted tissues. We will develop and implement precise ultrasound ablation and 3D ultrasound image guidance that is widely affordable, as an option to watchful waiting for patients with early stage prostate cancer and patients with localized focal or dominant tumor regions within the prostate. Ultrasound image guidance combined with information from biopsy maps and/or multi-parametric MRI will guide and precisely deliver this minimally invasive treatment device to the diseased regions of the gland. There are clinical differences of opinion with respect to treatment of microscopic disease. Here, it is important to emphasize that a localized treatment for focal prostate disease has been long sought after and that the standard of care for breast disease is conservative surgery followed by localized radiation, i.e. focal therapy. Our proposed focal disease therapy plus margin treatment is minimally invasive and readily followed by PSA testing. This precision image-guided therapeutic ultrasound approach can treat focal disease or whole gland, and may provide a needed alternative to those patients who have failed radiotherapy, are at high risk for surgery, or who seek alternatives for local control. Further, all other treatment options, including radical prostatectomy (open or robotic), radiotherapy, other thermal ablation, remain viable alternatives. The objective of this research is to develop new conformal high-intensity interstitial ultrasound therapy devices and spatial treatment control capabilities specific for prostate delivered using noninvasive image based treatment monitoring, and intraprocedural patient-specific treatment optimization for precision image-guided localized therapy for clinical study.