Prediction of early recurrence as a marker of surgical futility in pancreatic adenocarcinoma

Abstract

Background

Long-term survival after resection for pancreatic ductal adenocarcinoma (PDAC) is impaired by very high recurrence rates. When recurrence occurs within 6 months (early recurrence: ER) the benefit of surgery is equivalent to palliative chemotherapy in unresectable patients. Therefore, ER is a surrogate of surgical futility in PDAC.

Materials and methods

To investigate predictive factors of ER and its impact on survival, a training and a validation cohort of prospectively collected patients who underwent surgery for resectable or borderline-resectable PDAC were analyzed in two independent Pancreas Units during the same period. Logistic regression model on the training cohort identified independent predictors of ER, used to build a prognostic risk-score then tested on the validation cohort.

Results

Out of 176 patients in the training cohort, 21.6 % experienced ER, with significant impact on survival (OS: 9.7 months vs. 32.7 months for ER vs. late/no recurrence, respectively). At multivariable analysis, three independent risk factors for ER were identified: Ca19.9 > 100 U/mL, G3 tumors and lack of adjuvant chemotherapy. Based on such features the derived ER-score stratified three prognostic classes at incremental risk of ER (12 %, 35 % and 53 %) with different OS (31.1, 19.7 and 9.3 months, respectively, p < 0.001). The ER predictive score was then tested on a validation cohort of 242 patients, 22.3 % of whom underwent ER. Despite significant differences in tumor-related features, the score was able to discriminate among the predicted ER-risk classes (15 %, 27 % and 53 %, respectively) and forecast significantly different OS (5.8, 19 and 31.1 months, p > 0.001). The discriminative capability of the score in the two cohorts was similar (training AUC = 0.72 vs. validation AUC = 0.68, p = 0.28).

Conclusion

An externally validated clinical score, able to identify three prognostic classes at incremental risk of developing ER after resection of PDAC is provided. In patients at high risk of ER, prediction of surgical futility may help in decision-making.