Predictive factors for early relapse and survival in resected pancreatic cancer: A single institution experience
Authors: C. Saavedra Serrano, P. Reguera Puertas, O. Martínez Saez, F. Longo Muñoz, A. Barquín García, V. Albarrán Artahona, M. Villamayor Delgado, J. Molina Cerrillo, E. Corral de la Fuente, R. Martín Huertas, J. Serrano Domingo, V. Pachón Olmos, R. Ferreiro Monteagudo, M. Rodriguez Garrote, M. Vaz, R. Fuentes, C. Guillén-Ponce, A. Carrato
Journal: Annals of Oncology (2018)

Introduction: Pancreatic cancer is an aggressive tumor with a high mortality rate. Upon diagnosis only 15-20% of cases are amenable to surgery. Despite achieving a complete resection, relapse free survival (RFS) and prognosis remain poor (RFS 60% at 12 months and 20% 5-year overall survival (OS)). Several studies suggest that early recurrence predicts poor prognosis. However, cut-offs to define early relapse (ER) are variable between reports. The aim of our study is to propose an optimal cut-off for ER and finding clinicopathological factors that predict ER in resected pancreatic cancer. Methods: We conducted an observational retrospective study in the Ramón y Cajal University Hospital. Patients with resected pancreatic cancer between 2010 and 2016 were identified, and data was collected for predefined variables about patients and tumor clinicopathological characteristics, treatment procedures, oncological outcomes and follow up. Hazard ratio for overall survival was estimated for 3, 6, 9 and 12 months as potential cut-off points for ER. Univariate analysis with logistic regression were performed for factors potentially associated with ER risk. Significant factors identified were included into a predictive multivariate model using logistic regression. An estimative model for potential confusion factors was made for significant variables in the previous step. We obtained Kaplan-Meier curves and performed Cox regression for RFS and OS to confirm prognostic value of variables identified, and screened for confusion factors. Results: 67 patients who met inclusion criteria were identified. 54% were women. Median age at surgical intervention was 70 years old (range 44-85 years). 83.6% of tumors were located in the pancreatic head and R0 resection was achieved in 38.8%. 70.2% of patients received adjuvant chemotherapy (AC). At a median follow up of 39.2 months, relapse was confirmed in 56.7% of cases, of which 86.8% received further chemotherapy. The optimal cut-off point to define ER was 6 months in our cohort, as it showed the greatest difference in overall survival (HR 3.98; 95%CI 1.98-8.00). With this cut-off point, 2 year OS was 41% in the late relapse group and 10% in the ER group. AC and postoperative morbidity were identified as predictive factors for ER in the univariate analysis. The multivariate predictive model including these factors only showed a statistically significant difference for AC (OR 0.10; 95%CI 0.03-0.33; p 0,000). Additional test for confusion factors on AC effect was negative. Cox regression model showed a significant effect of AC both in RFS (HR 0.30; 95%CI 0.169-0.562) and OS (HR 0.303; 95%CI: 0.15-0.60). In a multivariate model, the effect of AC was maintained for RFS, but not for OS when adjusted for performance status. No other confusion factors were found. Conclusion: In our cohort, the best cut-off point to define early relapse in resected pancreatic cancer is 6 months. This cut-off point differentiates two groups with different prognosis. Patients receiving adjuvant chemotherapy were less likely to have an early relapse, regardless of other factors. Also, adjuvant chemotherapy impacts RFS and OS. Extrapolation of our results to general population is limited by its retrospective nature.