Serum CA 19-9 as a marker of resectability and survival in patients with potentially resectable pancreatic cancer treated with neoadjuvant chemoradiation

Abstract

Purpose: The role of carbohydrate antigen (CA) 19-9 in the evaluation of patients with resectable pancreatic cancer treated with neoadjuvant therapy prior to planned surgical resection is unknown. We evaluated CA 19-9 as a marker of therapeutic response, completion of therapy, and survival in patients enrolled on two recently reported clinical trials.

Patients and methods: We analyzed patients with radiographically resectable adenocarcinoma of the head/uncinate process treated on two phase II trials of neoadjuvant chemoradiation. Patients without evidence of disease progression following chemoradiation underwent pancreaticoduodenectomy (PD). CA 19-9 was evaluated in patients with a normal bilirubin level.

Results: We enrolled 174 patients, and 119 (68%) completed all therapy including PD. Pretreatment CA 19-9 <37 U/ml had a positive predictive value (PPV) for completing PD of 86% but a negative predictive value (NPV) of 33%. Among patients without evidence of disease at last follow-up, the highest pretreatment CA 19-9 was 1,125 U/ml. Restaging CA 19-9 <61 U/ml had a PPV of 93% and a NPV of 28% for completing PD among resectable patients. The area under the receiver-operating characteristics curve of pretreatment and restaging CA 19-9 levels for completing PD was 0.59 and 0.74, respectively. We identified no association between change in CA 19-9 and histopathologic response (P = 0.74).

Conclusions: Although the PPV of CA 19-9 for completing neoadjuvant therapy and undergoing PD was high, its clinical utility was compromised by a low NPV. Decision-making for patients with resectable PC should remain based on clinical assessment and radiographic staging.

Fig. 1

Receiver-operating characteristics (ROC) curves for pretreatment and restaging serum CA 19-9 levels as predictors of completing all therapy including pancreaticoduodenectomy. The area under the curve (AUC) and optimal cutoff values for pretreatment and restaging CA 19-9 were 0.59 (95% CI 0.47–0.71), 149 U/ml and 0.74 (95% CI 0.64–0.84), 61 U/ml, respectively

Fig. 2

Pretreatment serum CA 19-9 levels of patients stratified by resection and recurrence status at last follow-up. Of 78 patients with pretreatment CA 19-9 above normal, 52 (67%) underwent resection, of whom 15 (22%) died of another cause or had not recurred at last follow-up. Y-axis scale is Log₁₀. Horizontal line represents 37 U/ml

Fig. 3

Restaging serum CA 19-9 levels of patients stratified by resection and recurrence status at last follow-up. No patient with a restaging CA 19-9 ≥1,000 U/ml underwent resection. Y-axis scale is Log₁₀. Horizontal line represents 37 U/ml