Cancer Associated Macrophage-like Cells Are Prognostic for Highly Aggressive Prostate Cancer in Both the Non-Metastatic and Metastatic Settings

SIMPLE SUMMARY: Prostate cancer (PCa) patient mortality rates remain high in patients with aggressive disease and the overtreatment of indolent tumors remains a major issue. Prostate-specific antigen (PSA), a standard PCa blood biomarker, is limited in its ability to differentiate disease subtypes, which results in the overtreatment of non-aggressive indolent disease. Recently cancer-associated macrophage-like cells (CAMLs), a cancer-specific polyploid circulating stromal cell, was found in the blood of patients with PCa. Further, it has been suggested that engorged CAMLs ≥ 50 μm in cytoplasmic diameter are associated with aggressive tumor subtypes and worsened patient outcomes, which may aid PSA for patient stratification. To expand upon previous research, we hypothesized that monitoring CAML size, in combination with PSA, may aid in differentiating indolent, non-aggressive, and highly aggressive PCas by adding biological information that complements traditional clinical biomarkers, thereby guiding treatment for PCa. ABSTRACT: Despite advancements in the early-stage detection and expansion of treatments for prostate cancer (PCa), patient mortality rates remain high in patients with aggressive disease and the overtreatment of indolent disease remains a major issue. Prostate-specific antigen (PSA), a standard PCa blood biomarker, is limited in its ability to differentiate disease subtypes resulting in the overtreatment of non-aggressive indolent disease. Here we assess engorged cancer-associated macrophage-like cells (CAMLs), a ≥50 µm, cancer-specific, polynucleated circulating cell type found in the blood of patients with PCa as a potential companion biomarker to PSA for patient risk stratification. We found that rising PSA is positively correlated with increasing CAML size (r = 0.307, p = 0.004) and number of CAMLs in circulation (r = 0.399, p < 0.001). Over a 2-year period, the presence of a single engorged CAML was associated with 20.9 times increased likelihood of progression (p = 0.016) in non-metastatic PCa, and 2.4 times likelihood of progression (p = 0.031) with 5.4 times likelihood of death (p < 0.001) in metastatic PCa. These preliminary data suggest that CAML cell monitoring, in combination with PSA, may aid in differentiating non-aggressive from aggressive PCas by adding biological information that complements traditional clinical biomarkers, thereby helping guide treatment strategies.