Principal Investigators: Phuoc Tran, MD, PhD (Johns Hopkins University), Kenneth Pienta, MD (Johns Hopkins University)

Co-Investigators: Ana Kiess, MD, PhD (Johns Hopkins University), Hao Wang, PhD (Johns Hopkins University), Alexander Wyatt, PhD (University of British Columbia)

Description: 

• Oligometastatic prostate cancer is an advanced disease state in which men have fewer than five sites of metastasis, but are still thought to be potentially curable.
• Phuoc Tran has previously demonstrated that targeting sites of oligometastatic prostate cancer with stereotactic ablative radiation (SABR), a highly focused form of radiation therapy, is feasible and prolongs progression-free survival. However, SABR alone was not curative in most men, and patients often progressed due to outgrowth of tumor deposits, particularly in the bone, that were too small to be detected by molecular imaging at the beginning of the study.
• Tran and team are conducting two clinical trials in patients with oligometastatic prostate cancer testing whether combining SABR with other systemic radioactive treatments can improve outcomes of patients with oligometastatic prostate cancer. The RAVENs trial will test SABR alone vs. in combination with radium-223. The BLUE JAE trial will test SABR in combination with the PSMA-targeted radionuclide therapy, ¹⁷⁷Lu-PSMA.
• In this project, Dr. Tran and team will use samples from the patients on these trials to investigate whether the levels of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) associate with patient outcomes.
• Epithelial-mesenchymal transition (EMT) is a phenomenon in which tumor cells change their phenotype to acquire invasive and metastatic properties. Whether low expression of EMT markers is associated with an attenuated metastatic phenotype of oligometastasis and improved outcomes of patients in these trials will be investigated.
• Immune responses may improve the efficacy of radiation therapy. Whether specific T-cells repertoire at the start of therapy in these trials may impact clinical outcomes will be determined.
• Finally, the frequency of inherited mutations in DNA repair genes in men with oligometastatic prostate cancer will be determined.
• If successful, this project will improve the management and understanding of the biology of oligometastatic prostate cancer.

What this means to patients:  Oligometastatic prostate cancer is thought to be a potentially curable state of prostate cancer, in which five or fewer metastases are present. Dr. Tran and team will conduct two clinical trials in men with oligometastatic prostate cancer to test the efficacy of stereotactic ablative radiation (SABR), a highly focused form of radiation therapy combined with other systemic radioactive treatments, and will investigate tumor biology and biomarkers of outcomes in these patients. This may lead to a new, curative treatment paradigm for men with oligometastatic prostate cancer.