Peripheral monocyte ratio as a predictive biomarker for metastasis-directed therapy in prostate cancer: insights from an exploratory study

Traditionally, androgen deprivation therapy (ADT) alone was the standard treatment for oligometastatic prostate cancer. However, stereotactic body radiotherapy (SBRT) for metastasis-directed therapy (MDT) in the hormone sensitive setting is demonstrating improved outcomes. Despite this, not all patients will experience a durable response to MDT. The discovery of pre-treatment biomarkers to predict patient outcomes are needed to further improve management in this setting. In this randomized study, peripheral blood mononuclear cells were collected and analyzed using flow cytometry from 26 hormone sensitive oligometastatic prostate cancer patients that were recruited and randomly assigned to receive either intermittent androgen deprivation therapy (iADT) alone or MDT in the form of iADT+SBRT as part of a larger clinical trial. In patients treated with MDT, a high peripheral ratio of CD14high (classical) to CD14low (non-classical) monocytes at pre-treatment was significantly associated with complete biochemical response (PSA becoming ≤ 0.02 ng/mL) and freedom from biochemical progression (PSA nadir + 2 ng/mL). In contrast, the association was absent in patients treated with iADT alone, suggesting that SBRT may play a significant role in mounting an immune response, resulting in improved oncological outcomes. Furthermore, single-cell RNA sequencing of prostate cancer metastases suggested that classical monocytes from early responder patients may exhibit an elevated pro-inflammatory and chemokine-responsive transcriptional program. Together, these preliminary findings suggest the potential of monocyte ratios as an early predictive biomarker for MDT. If validated, this could potentially identify poor responders to MDT for consideration of additional systemic treatments.