? DESCRIPTION (provided by applicant): Metastatic castration-refractory prostate cancer (CR-PC) patients have poor prognosis with median survival of approximately 14 months. 10-20% of all prostate cancer patients develop metastatic CR-PC within 5 years of initial diagnosis, and therefore, improved therapeutic strategies are needed. Oligometastasis describes a clinical state where metastases are limited in number, and metastatectomies for various oligometastatic solid tumors can lead to long-term survival. Stereotactic Ablative Radiotherapy (SABR) is a noninvasive therapy with local control (LC) similar to surgery. In our experience, oligometastatic prostate cancer patients (65% were CR-PC) experienced 100% LC at 6 months with SABR with corresponding decline in their PSA. 11C-Choline PET/CT was FDA-approved in recurrent metastatic prostate cancer patients, and prior restaging studies have validated the sensitivity, specificity, positive predictive value, and negative predictive value of Choline PET at 85-100%, 76-96%, 76-91%, and 81-100%, respectively. Therefore, 11C- Choline PET/CT may help to identify true oligometastatic CR-PC patients. Objectives/Hypothesis: The combination of 11C-Choline PET/CT and SABR may improve true oligometastatic (CR-PC) patient selection, alter their clinical management (i.e., from noncurative to curative intent with the addition of SABR), and impact natural disease progression (improve LC, PSA progression-free survival and overall survival [OS]). SABR may also induce anti-prostate cancer immunity, which could be amplified into long-term protective immunity with immune-regulation inhibitors (e.g., ipilimumab, anti-PD1/PD-L1). Specific Aims/Study Design: We propose a prospective single arm phase II clinical trial to assess the role of 11C-Choline PET/CT and SABR in metastatic CR-PC patients with the goal of improving clinical outcomes (Aim 1). We also propose a translational study in Aim 2 to explore the induction anti-prostate cancer immunity elicited by SABR treatments. The confirmation of the ability of SABR to induce anti-prostate cancer immunity would provide a robust rationale to combine SABR and immunomodulating agents (i.e., checkpoint inhibitors) in widespread castration- and chemotherapy- resistant metastatic prostate cancer. The proposed biomarker (CD11ahighPD-1high CD8+ T cells) may improve identification of potential responders to the combined SABR and anti-PD1 therapy. Impact: The incorporation of 11C-Choline PET/CT in the selection of oligometastatic CR-PC patients whose limited metastases are amenable to SABR may improve OS. If our hypothesis is proven successful, there would be a paradigm shift in the clinical management of these patients (i.e., from noncurative to curative intent). The in situ induction of anti-prostate immunity by SABR, if confirmed, would form a robust rationale for the combination of SABR and immunomodulating agents in future clinical trials.
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.