Identification and Treatment of Microscopic Residual and Recurrent Disease in Prostate Cancer Using in Vivo Microfabricated Sensors and Targeted Biologics
Abstract
Scientific Objective and Rationale: Complete excision is essential for optimal local control for many early-stage cancer therapies; however, microscopic disease, which extends from the tumor and cannot be seen with current imaging or felt, is often left behind. This is called microscopic residual disease, or MRD, and is known to lead to increased local recurrence in almost every cancer subtype and may increase cancer mortality. MRD is particularly important in prostate cancer, tripling the rate of recurrence. Approximately 11%-50% of prostate cancers are found to extend beyond the prostate, leading to MRD. Unlike other cancer sites, like breast cancer, re-operation is not an option due to the morbidity of re-excising tissue in the prostate bed. Therefore, the only option is 6 weeks of post-operative radiotherapy (PORT), with possible long-term androgen deprivation, resulting in significant cost ($30,000 to $60,000) and toxicity to the patient. Despite additional therapy, the outcomes remain poor, with only 45% of patients disease free at 4 years after treatment. Therefore, a method to intraoperatively assess MRD to guide complete resection at the time of initial surgery is needed to improve clinical outcomes in prostate cancer. Unfortunately, because sensitivities down to ~1,000 cells are needed to image MRD, no current imaging modality exists to evaluate MRD in a real-time, intraoperative setting, where further resection can take place. Currently, microscopic disease is only definitively identified in the pathology lab, where cancer cells in excised tissue samples are molecularly identified using sensitive antibodies with a microscope. Multiple efforts at developing tools for intraoperative visualization of MRD have been attempted, but none leverage a combination of molecular identification of tumor cells and form factor small enough to image the entire tumor bed and therefore have poor sensitivity and are not widely adopted. Together with a team of physicians and interdisciplinary experts in electrical engineering, and clinical and biological prostate cancer research, this project builds upon our novel fluorescent imaging technology to introduce a new paradigm in medical imaging: live intraoperative visualization of MRD using molecular markers to guide real-time surgical resection. Our approach is to (a) label tumor cells in vivo using a pre-operatively injected fluorescently conjugated small molecule that specifically binds to prostate-specific membrane antigen (PSMA), developed here at the University of California, San Francisco, and (b) develop a custom microfabricated fluorescent imager capable of being placed within the tumor bed to visualize MRD in vivo, essentially bringing the tools of the pathology lab into the live tumor bed. Applicability to Research to Patients: Many patients who undergo radical prostatectomy as the definitive treatment for prostate cancer and are left with MRD. Without treatment, patients develop distant metastases in 8 years, and die from prostate cancer 5 years later. The only existing therapy is PORT with the majority of patients still recurring within 4 years. Therefore, the optimal solution is to eliminate MRD by identifying and resecting it at the time of initial surgery. This proposal will help all patients, but in particular intermediate and high-risk prostate cancer patients, where the risk of MRD ranges from 30% to 50%. By eliminating the occurrence of MRD, these patients can have their chance of prostate cancer returning reduced by a factor of 2 to 3. Because the device is used during the initial operation, there is no significant additional morbidity or risk for the patient. Contributions to Advancing the Field of Prostate Cancer Research: At UCSF, the high volume of prostate cancer patients treated by both surgery and radiation will enable us to evaluate the device in a clinical trial setting and rigorously analyze the effects of identifying MRD intra
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510531
Entities
People
- Moshiur Anwar
Organizations
- United States Army
- University of California, San Francisco