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 ~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.