Persistent Circulating Tumor Cells at 1 Year After Oncologic Resection Predict Late Recurrence in Pancreatic Cancer

Objective: The aim of the study was to assess the association between persistent circulating tumor cells (CTCs) and subsequent recurrence in patients who were clinically recurrence free similar to 12 months postoperatively. Background: Circulating tumor cells have been proposed as biomarkers to predict survival in pancreatic cancer. Some patients demonstrate persistent CTCs postoperatively, which could represent minimal residual disease. Methods: Patients from previously published prospective circulating tumor cell in pancreatic cancer trial without clinical evidence of recurrence 12 months postoperatively and CTC testing performed 9 to 15 months postoperatively were included. The presence of epithelial and transitional CTCs (trCTCs) was evaluated as predictor of recurrence. Kaplan-Meier curve, log-rank test, and Cox model were used for survival analysis. Results: Thirty-three of 129 eligible patients (circulating tumor cell in pancreatic cancer trial) were included. The trCTC-positive and negative patients were well balanced in clinicopathologic features. Patients with trCTCs had a recurrence rate per-person-month of 10.3% compared with 3.1% in trCTCs-negative patients with a median time to recurrence of 3.9 versus 27.1 months, respectively. On multivariable analysis, trCTCs positivity was associated with higher risk of late recurrence (hazard ratio: 4.7, 95% CI, 1.2-18.3, P = 0.024). Fourteen (42.4%) patients recurred during the second postoperative year. One-year postoperative trCTCs positivity was associated with a higher rate of recurrence during the second year (odds ratio:13.1, 95% CI, 1.6-1953.4, P = 0.028, area under curve = 0.72). Integrating clinicopathologic features with trCTCs increased the area under curve to 0.80. A majority of trCTCs-positive patients (N = 5, 62.5%) had multisite recurrence, followed by local-only (N = 2, 25.0%) and liver-only (N = 1, 12.5%) recurrence. This was in striking contrast to trCTCs-negative patients, where a majority (N= 6, 66.7%) had a local-only recurrence, followed by liver-only (N = 2, 22.2%) and multisite (N = 1, 11.1%) recurrence. Conclusions: In patients deemed to be clinically disease-free 12 months postoperatively, trCTCs positivity is associated with higher rates of subsequent recurrence with distinct patterns of recurrence. CTCs could be used a putative biomarker to guide patient prognostication and management in pancreatic cancer.