Transitional Subtype of Circulating Tumor Cells in Early Post-Operative Period of 5-Year Survivors Following Resection of Pancreatic Ductal Adenocarcinoma

Objectives The objective was to assess the ability of circulating tumor cells (CTCs) to predict long-term survival (LTS, >5 years after resection) in pancreatic ductal adenocarcinoma (PDAC). Summary of background data Predictors of LTS remain poorly understood in PDAC. Methods Patients enrolled in the prospective CLUSTER Trial for serial assessment of CTCs, undergoing PDAC resection were included (2016-2018). Number of epithelial (eCTCs) and transitional (trCTCs) CTCs were serially assessed. Clinicopathological factors and CTC characteristics associated with LTS were identified and their ability to predict LTS was assessed. Results In 133 patients, 41% and 82% received neoadjuvant and/or adjuvant therapy, respectively. LTS was achieved by 17% patients. Nodal disease and perineural invasion (PNI) were present in 62%, and 80% of patients, respectively. Preoperatively eCTCs and trCTCs were observed in 97% and 68% of patients as compared to 77% and 27% postoperatively. PNI (OR:0.19,95%CI:0.06-0.60), nodal disease (OR:0.28,95%CI:0.09-0.82), and postoperative trCTCs (OR:0.04,95%CI:0.01-0.38) were independently associated with LTS. A clinical score based on PNI and nodal disease demonstrated an AUC of 0.79 (95%CI:0.69-0.89) in predicting LTS. Addition of postoperative trCTC into a translational score demonstrated an AUC of 0.84 (95%CI:0.75-0.92). Upon internal validation the clinical and translational scores had AUCs of 0.78 (95%CI:0.67-0.89) and 0.84 (95%CI:0.73-0.92), respectively (p<0.001). Conclusions Patients with residual postoperative trCTCs are unlikely to achieve LTS and trCTCs emerge as one of the strongest predictors of LTS in resected PDAC. Inclusion of postoperative trCTC status to clinicopathological factors improves our ability to predict LTS.