In-Depth Analysis of Post-recurrence Survival in Resected Pancreatic Ductal Adenocarcinoma: A Cohort Study

Background Recurrence after curative-intent resection of pancreatic ductal adenocarcinoma (PDAC) is frequent, however post-recurrence survival (PRS) may vary widely. Aims To analyze in depth PRS and identify the prognostic factors associated with it. Methods Retrospective cohort study including patients with PDAC recurrence after pancreatectomy. PRS was estimated with the Kaplan Meier method in the whole cohort and in subgroups based on performance status (ECOG-PS) at recurrence, timing, pattern, treatment of recurrence. Prognostic factors of PRS were evaluated through a Cox regression model. Results Seventy patients who underwent pancreatic resection (pancreatoduodenectomy, n=49; distal pancreatectomy, n=19; total pancreatectomy, n=2), and experienced PDAC recurrence, were included. R0, pN+ and perineural invasion rates were 72.9%, 67.1% and 94.3% respectively. Neoadjuvant and adjuvant chemotherapy were administered in 34.3% and 70% respectively. Recurrences were in multiple sites (51.4%), peritoneal-only (18.6%), hepatic-only (7.1%), isolated local (11.4%), pulmonary-only (1.4%). Early recurrence (<1 year after pancreatectomy) occurred in 41 cases (58.6%). Mean recurrence-free survival was 14.0 months; mean PRS was 13.0 months in the whole cohort. In subgroup analyses, patients with low ECOG-PS (0-1) had longer PRS than those with high ECOG-PS (>1) (log-rank=42.1; p>0.001). Conversely, PRS was similar in patients in early vs. late recurrences (log-rank=1.110; p=0.292) and by site of recurrence (log-rank=2.39; p=0.664). Recurrence treatment with chemotherapy, radical surgery or both was associated with longer PRS compared to radiotherapy, palliative surgery or best supportive care (log-rank=35.7; p<0.001). Cox regression analysis found R0 resection after index pancreatectomy (HR=0.44), low ECOG-PS at recurrence (HR=0.18) and treatment of recurrence by chemotherapy, surgery or both (HR=0.34), to be independently associated with a lower cumulative risk of death after recurrence. Borderline/locally-advanced PDAC and multisite recurrences tended toward worse PRS. Conclusion PRS seems influenced by patients' conditions at recurrence and the feasibility of effective treatments (including surgery), rather than only by surrogates of biology of the disease (initial resectability status, timing/pattern of recurrence).