Defining and Predicting Early Recurrence for Optimal Treatment Strategies for Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: An International Multicenter Study

Background: Early recurrence in intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is poorly defined. Predictors are lacking and needed for patient counseling, risk stratification, and postoperative management. This study aimed to define and predict early recurrence for patients in resected IPMN-derived PDAC and guide management.

Methods: A lowest p value for survival after recurrence (SAR) was used to define early recurrence in resected IPMN-derived PDAC from five international centers. Overall survival (OS) and SAR were compared using log-rank tests. A multivariable logistic regression identified odds ratios (ORs) with 95 % confidence intervals (CIs) for early recurrence. Rounded ORs were used to stratify patients into low-, intermediate-, and high-risk groups using upper and lower quartile score distributions. Adjuvant chemotherapy was assessed by Cox regression and log-rank tests for OS in risk groups.

Results: Recurrence developed in 160 (42 %) of 381 patients. Early recurrence was defined at 10.5 months and observed in 61 patients (38 % of recurrences). The median SAR for the patients with early recurrence was 8.3 months (95 % CI, 3.1-16.1 months) compared with 12.9 months (95 % CI, 5.2-27.5 months) for the patients with late recurrence. The independent predictors of early recurrence were CA19-9 (OR, 3.80; 95 % CI, 1.54-9.41) and N2 disease (OR, 7.29; 95 % CI, 3.22-16.49). The early recurrence rates in the low-, intermediate-, and high-risk groups were respectively 1 %, 14 %, and 32 %. Adjuvant chemotherapy was associated with improved OS only for the high-risk patients (hazard ratio, 0.50; 95 % CI, 0.32-0.79).

Conclusion: In IPMN-derived PDAC, the optimal cutoff for early recurrence is 10.5 months. Both CA19-9 and N stage predict early recurrence. Adjuvant chemotherapy is associated with survival benefit only for high-risk patients.