A Nanotechnology Solution for Early Detection of Micrometastatic Prostate Cancer After Radical Prostatectomy
Abstract
Background: Radical prostatectomy (RP) has remained an important means of addressing early and localized prostate cancer (PCa). However, 30% of patients experience recurrence after RP that is typically detected by serum PSA testing. This unique group of patients can still be cured by post-operative radiation therapy, termed salvage radiotherapy (SRT), provided there is an absence of metastatic disease. The use of SRT is associated with improved, long-term freedom from cancer recurrence. Unfortunately, 50% of patients will continue to progress after SRT. This is likely due to the fact that the disease has already spread beyond the prostate bed while not yet detectable by current imaging methods (i.e., micro-metastatic PCa). These unfortunate patients will suffer from the side effects of SRT, including damage to the rectum and bladder without having the desired long-term treatment benefit. Therefore, identification of these patients before SRT would be very important. Recently, our team has developed the Thermoresponsive (TR)-NanoVelcro assay, which allows for the capture and release of circulating tumor cells (CTCs) from blood with intact RNA information. We combined this technology with Droplet Digital PCR to accurately quantify three PCa-specific RNA (i.e., PSA, PSMA, and SChLAP1) markers in the purified CTCs. We have found that the presence of these RNA markers strongly associates with PCa that has already metastasized. We believe that these RNA markers can be detected even before metastases can be found on the imaging scans. By studying CTCs, our team has been able to obtain insight into the underlying cancer using a blood test that could be used to optimize patient selection for SRT. Applications and Benefits: 1. We believe this simple, existing, non-PSA blood test can be used in the clinic to identify patients who may need additional workup prior to initiation of SRT. This would include more advanced imaging whose results could strongly impact treatment planning to maximize benefit and minimize harm. 2. The technology that we developed can be broadened to study other RNA markers that are associated with PCa behavior using blood testing as a complement to tissue-based studies. Projected Time to Patient-Related Outcomes: This project focuses on using banked and annotated patient samples to improve our ability to relate our biological findings with clinical outcomes. Thus, any and all results are patient-related and clinically relevant. NanoVelcro devices have been under review by the Food and Drug Administration (FDA) as a CTC test, and the TR-NanoVelcro system is preparing for the FDA 501K submission. Thus, positive results from these studies will affect patients as this research program is being completed. Impact on Advancing the Field of Prostate Cancer Research and Addressing the Overarching Challenges in Prostate Cancer: 1. We will develop a test that can be useful for detecting PCa-specific RNA markers in blood, providing prostate cancer researchers a simple solution to study the evolving disease. 2. The RNA markers that we tested are related to disease spread and aggressive behavior. We hope to use these markers to define the biology of lethal prostate cancer to reduce death. 3. This proposal will create a new test for identifying patients who are not suitable for SRT. These patients can pursue other imaging assessments or treatments, avoiding the unnecessary side effects of SRT, therefore improving the quality of life for survivors of prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910390
Entities
People
- Edwin M Posadas
Organizations
- Cedars-Sinai Medical Center
- United States Army