Preoperative Soluble AXL in Plasma Predicts Futility of Resecting Pancreatic Ductal Adenocarcinoma

TL;DR

High levels of a blood protein called sAXL before surgery may predict which pancreatic cancer patients are unlikely to benefit from surgery.

Contribution

sAXL is shown to be a better predictor of early mortality after surgery than the current standard biomarker CA19-9.

Findings

Patients with high preoperative sAXL levels had 2-3 times higher risk of death within six months after surgery.

sAXL outperformed CA19-9 in predicting early mortality with a cut-off of 40.26 ng/mL.

sAXL remained a significant predictor of mortality even when accounting for tumor grade and surgical margin status.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer mortality in Canada. Radical surgery combined with chemotherapy is the only hope for a cure, but many of those undergoing surgery will still recur and die within 6–24 months. We examined soluble AXL (sAXL), a protein shed into the blood from PDAC tumours, for its ability to distinguish risk for death within the first six months post-surgery. Six-month mortality was 2 to 3 times more likely if they had high levels of sAXL in their blood before surgery. This study supports further research into more complex models to predict early mortality after surgery, to guide pre-operative conversations and identify those who should undergo more intensive follow-up after resection or those who would not benefit at all from surgery.

Surgical resection combined with chemotherapy offers the best chance of survival in pancreatic ductal adenocarcinoma (PDAC), but many will experience recurrence and early mortality. We examined soluble AXL (sAXL), a blood protein, for its ability to predict 6-month mortality after resection and compared it to CA19-9. Fifty-four patients with PDAC who underwent tumour resection were analyzed to assess biomarker performance and identify optimal cut-off levels. The cut-off for sAXL was 40.26 ng/mL (sensitivity 0.729; specificity 0.643), while it 253.3 U/mL for CA19-9 (sensitivity 0.591; specificity 0.621). Patients with sAXL > 40.26 ng/mL had a non-significant trend toward worse survival (log-rank p = 0.088). Univariate Cox regression revealed that high tumour grade (3 + 4) and positive resection margin significantly predicted early mortality. Multivariate Cox regression showed that sAXL > 40.26 ng/mL remained associated with 6-month mortality (hazard ratio 2.42, bootstrap 95% CI 1.15–5.65, p = 0.020), independent of high tumour grade (hazard ratio 4.02, bootstrap 95% CI 1.68–13.2, p = 0.002). These findings suggest that a preoperative blood test (sAXL) has utility for predicting futile surgery beyond the current standard, CA19-9, and can be incorporated into larger models to assist in risk stratification and follow-up planning.

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