Cancer Associated Macrophage Like Cells Predict Aggressive Disease In Local And Metastatic Prostate Cancers

Abstract Background: Prostate cancers (PC) are intrinsically complex, with few prognostic biomarkers that differentiate aggressive and indolent disease. Cancer associated macrophage like cells (CAMLs) have shown to be significant independent prognostic indicators for poor survival in tumors if engorged to ≥50μm. However, no group has examined CAMLs' in PC. In this prospective pilot study, we analyzed PSA & ≥50μm CAML presence in (n=51) Stage I-III & (n=41) metastatic PC (mPC) prior to the start of new treatments to examine CAMLs' on outcomes. We found that ≥50μm CAML presence significantly predicted worse patient survival in mPC. These preliminary results suggest that CAMLs may serve as a cheap, non-invasive prognostic biomarker that predicts for worse outcomes in both local & mPC prior to new therapies. Methods: We prospectively recruited (n=92) PC patients in this pilot study to examine CAML's prognostic significance in non-metastatic (stages I-III) and mPC. Of (n=92) total patients, 15% (n=14/92) were stage I, 32% (n=29/92) stage II, 9% (n=8/92) stage III, and 45% (n=41/92) Stage IV. Prior to the induction of new therapy or first line therapy for newly diagnosed patients, 7.5mL peripheral baseline (BL) blood was collected. Blood was filtered via CellSieveTM microfiltration, which excludes cells by size ≥7μm. In parallel, changes in PSA was monitored to compare prognostic significance against ≥50μm CAMLs. Wilcoxon univariate analysis was used to analyze ≥50μm CAMLs and PSA in progression free survival (PFS) and overall survival (OS). Results: CAML's were identified in 78.9% (n=71/90) of available BL samples, with two samples failing from clotting. Stage I-III patients had an average of ~3 CAMLs/7.5mL blood, whereas mPCs contained ~6 CAMLs/7.5mL. Average CAML size increased linearly with advancing stage of disease with stage I patients averaging 23μm, stage II 33μm, stage III 65μm, and stage IV 78μm. Of available BL samples, 41% (n=38/90) patients with ≥50μm CAMLs significantly predicted for worse PFS (HR=10.0, p<0.001, 95%CI=0.07-0.31) and OS (HR=34.2, p<0.001, 95%CI=0.03-0.21). Further, ≥50μm CAMLs significantly predicted for poorer survival in mPC with PFS (HR=9.4, p=0.028, 95%CI=0.18-0.84) and OS (HR=5.1, p=0.003, 95%CI=0.07-0.53), but only non-significantly trended in non-metastatic disease. Initial analysis of PSA found that high PSA at BL was a significant predictor for worse outcomes in patients, while changes in PSA was not a predictor. Conclusions: CAMLs have shown potential as a predictive non-invasive blood based biomarker across multiple solid malignancies, and here we compared this biomarker in PC. While preliminary, these data suggests that engorged CAML presence prior to the start of new treatment may be a statistically significant predictor of survival in both the local and metastatic setting, and a larger validation cohort should be established. Citation Format: Daniel J. Gironda, Raymond Bergan, R K. Alpaugh, Daniel C. Danila, Tuan L. Chuang, Brenda Y. Hurtado, Thai Ho, Cha-Mei Tang, Daniel L. Adams. Cancer associated macrophage like cells predict aggressive disease in local and metastatic prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 357.