208 - Assessment of Circulating Tumor Cells in Oligometastatic Castration-Sensitive Prostate Cancer Patients from the ORIOLE Trial

S. Bazyar¹, P. Sutera², M. P. Deek³, J. Wang⁴, R. Phillips⁵, N. Radwan⁴, C. H. Marshall⁶, M. V. Mishra⁷, Z. H. Rana⁸, J. K. Molitoris¹, Y. Kwok¹, M. J. Ferris¹, S. Gupta⁹, R. Wenstrup¹⁰, T. L. DeWeese¹¹, D. Song², K. Pienta⁶, E. S. Antonarakis¹², A. P. Kiess⁴, and P. T. Tran¹³; ¹Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, ²Johns Hopkins University School of Medicine, Baltimore, MD, ³Rutgers Cancer Institute of New Jersey, Department of Radiation Oncology, New Brunswick, NJ, ⁴Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, ⁵Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ⁶Johns Hopkins Medicine, Baltimore, MD, ⁷Maryland Proton Treatment Center, Baltimore, MD, ⁸University of Maryland, Baltimore, MD, ⁹Epic Sciences, San Diego, CA, United States, ¹⁰Epic Sciences, San Diego, CA, ¹¹Johns Hopkins University School of Medicine, Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, ¹²University of Minnesota, Minneapolis, MN, ¹³University of Maryland School of Medicine, Baltimore, MD

Purpose/Objective(s): Metastasis-directed therapy (MDT) can alter the natural history of oligometastatic castration-sensitive prostate cancer (omCSPC) as shown in the STOMP, ORIOLE, and SABR-COMET phase II randomized trials. However, patients with omCSPC represent a diverse population with varying outcomes, necessitating the identification of prognostic and predictive biomarkers to aid in outcome prediction. Circulating tumor cells (CTCs), shed from solid tumors, are believed to play a crucial role in cancer metastasis. This study aimed to enumerate CTCs and assess the clinical significance of different CTC subtypes in omCSPC patients undergoing stereotactic ablative body radiotherapy (SABR) MDT from the ORIOLE trial. Materials/

Methods: ORIOLE randomized men with recurrent omCSPC (1-3 metastases) to observation (OBS) vs SABR MDT. Samples were prospectively collected at baseline (D0) and 6-mos (D180) and analyzed on Epic Sciences CTC platform for CTC number and expression of androgen receptor (AR), PSMA or vimentin (VIM). Biochemical progression was PSA rise >2 ng/mL or 25% above nadir. Metastasis-free survival (MFS) was defined by conventional imaging. Patient characteristics were compared by Chi-square and Mann-Whitney U-tests. Median cutoffs for high and low CTC levels were used. Survival curves were generated by the Kaplan-Meier method and evaluated by log-rank test. Predictive factors were assessed using Cox regression with treatment-by-covariate interaction.
Results: Eighty-one CTC samples were collected from ORIOLE patients with a median follow-up of 41.7-mos: 41 at baseline (14 OBS, 27 SABR) and 40 at D180 (14 OBS, 26 SABR). At D0, 38/41 men had CTCs detected (AR+= 6, PSMA+=13, VIM+=7) and 37/40 at D180 (AR+= 9, PSMA+=8, VIM+=6). There was no association between presence of AR+, PSMA+ or VIM+ CTCs or CTC level (low vs high) with age, baseline Gleason, pre-MDT PSA, site of metastasis or initial treatment modality. The median percentile of PSMA+ CTCs at D0 was higher in patients with biochemical progression and metastatic events (P=0.02 for both). Baseline high CTC levels, PSMA+ CTCs and rise in the level of CTCs at D180 compared to D0, showed a significantly worse biochemical progression free survival (bPFS) and MFS (all P<0.05). CTC were found to be predictive of response to MDT as patients with low CTCs (HR: .15, 95% CI 0.04 to 0.66; P=.004) but not high CTCs (HR: 0.66, 95% CI, 0.26 to 1.69; P= 0.386) had improved bPFS with SABR MDT over OBS (P_interaction=.048).
Conclusion: High levels of CTCs and presence of PSMA+ CTCs at baseline as well as dynamic increase in CTC levels over time were associated with worse bPFS and MFS in omCSPC. Lower levels of CTCs were a positive predictive factor for response to SABR MDT in the ORIOLE trial. Validation of these findings in a separate cohort are needed and if confirmed nominate a useful liquid biomarker to direct SABR MDT in omCSPC.