Transitional Circulating Tumor Cells Hold Predictive Value for Patients Undergoing PDAC

Rompen IF, Habib JR, Marchetti A, et al. Transitional Type Circulating Tumor Cells Predict Systemic Recurrence and Support Risk Stratification for Chemotherapy After Resection of Pancreatic Ductal Adenocarcinoma: Long-term Outcomes of the CLUSTER Trial. Ann Surg. December 2025.

This prospective analysis of the CLUSTER trial evaluated the prognostic and predictive value of transitional circulating tumor cells (trCTCs) in patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). 

Among 123 patients with long-term follow-up, preoperative trCTCs were detected in 67% and showed a linear association with the risk of systemic recurrence, independent of CA19-9, with no meaningful correlation between the two biomarkers. While both preoperative trCTC burden and CA19-9 levels predicted systemic recurrence, given that they have no relationship with each other they will likely have a synergistic role in predicting outcomes.

Postoperative trCTC status emerged as a strong indicator of minimal residual disease. trCTCs were detected after resection in 27% of patients, nearly all of whom developed recurrence, predominantly systemic, with significantly shorter time to recurrence and worse overall survival compared with trCTC-negative patients. Patients who cleared trCTCs after surgery had outcomes comparable to those who were trCTC-negative both pre- and postoperatively, whereas persistent trCTC positivity identified a high-risk subgroup.

Importantly, trCTC status stratified benefit from adjuvant chemotherapy. After multivariable adjustment, patients with postoperative trCTC positivity derived a significant overall survival benefit from adjuvant chemotherapy, whereas no clear benefit was observed in trCTC-negative patients, with a statistically significant interaction between trCTC status and treatment effect. 

Collectively, the data supports integrating trCTC assessment into perioperative risk stratification to identify patients at highest risk for systemic recurrence and those most likely to benefit from adjuvant chemotherapy, thereby advancing a more personalized treatment approach in resected PDAC.