Novel Biomarkers to Direct Stereotactic Ablative Radiotherapy in Castration-Sensitive Oligometastatic Prostate Cancer
Abstract
The importance of treating all tumor deposits in a patient with metastatic disease that has spread to only a limited number of areas also known as oligometastatic disease is now backed by small studies. Our overarching hypothesis is that visible prostate tumors support the growth of and help nurture future distant metastatic sites that are not yet visible or microscopic. Our recently completed Baltimore ORIOLE randomized trial of stereotactic ablative radiation (SABR) alone (highly focused, high-dose radiation) versus observation in oligometastatic prostate cancer (PCa) final data confirm this concept. Our ORIOLE trial in combination with prior data suggest one dominant mode of return of disease after SABR treatment is from microscopic disease not visible prior to treatment, especially those with bone metastases. In addition, we also hypothesize that biology programs that allow for development of the embryo are co-opted by the tumor cells and determine the metastatic potential of PCa. These are important early clinical data suggesting the existence of an oligometastatic state and the importance of therapies such as SABR in the management of these patients. Radiopharmaceutical therapy (RPT) approaches or radioactive agents that are injected into the blood have not been applied in the oligometastatic space; thus, the opportunity to target micrometastatic disease in conjunction with SABR has the potential to provide a curative paradigm for patients with oligometastatic PCa. We are soon to launch a second randomized trial to examine whether the addition of RPT to SABR will improve on outcomes for men with oligometastatic PCa. Now one of the most important open questions is to define the oligometastatic patients who may benefit the most from SABR and RPT. To answer this question, imaging-based and blood-based biomarkers such as PET-CT imaging, circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) may improve our ability to characterize which patients benefit most from treatment. In this proposal, we are testing whether any of these biomarkers can help us determine which men with oligometastatic PCa benefit the most from SABR with or without RPT. Collectively, these highly novel and innovative experiments will help address the critical question of whether intensive local therapy in the form of SABR combined with RPT in men with oligometastatic PCa can prolong survival free of disease progression and reveal novel non-invasive methods of disease monitoring. The studies detailed in our proposal have the potential to significantly impact the management of metastatic PCa in a rapid and broad fashion. We are directly addressing the FY20 PCRP Overarching Challenges to “develop treatments that improve outcomes for men with lethal prostate cancer” and “define the biology of lethal prostate cancer to reduce death.” These studies could ultimately provide progress toward the elimination of death from prostate cancer and enhance the well-being of Service members, Veterans, and all the men and their families who are experiencing the impact of the disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110296
Entities
People
- Phuoc Tran
Organizations
- Johns Hopkins University
- United States Army