RESECTION RATE AND SURVIVAL AFTER NEOADJUVANT THERAPY FOR BORDERLINE RESECTABLE AND LOCALLY ADVANCED PANCREATIC CANCER: A PROSPECTIVE COHORT STUDY
Simone Serafini*, Lucia Moletta, Elisa Sefora Pierobon, Alberto Ponzoni, Giovanni Capovilla, Alfredo Piangerelli, Michele Valmasoni, Cosimo Sperti
University of Padova, Padova, Italy
Introduction
In the last decade, a strategy of neoadjuvant therapy (NAT) followed by conversion surgery has been tested and is increasingly used in the treatment of primarily unresectable pancreatic adenocarcinoma (PDAC). The introduction of new chemotherapeutic regimens, such as folfirinox (FFN) and gemcitabine plus albumin-bound paclitaxel (GEMPAC), have brought encouraging results in terms of downstaging, conversion to resectability and survival. Randomized clinical trials (RCTs) are lacking on this topic. The aim of this study is to evaluate the impact of NAT on borderline resectable (BR) and locally advanced (LAC) pancreatic cancer.
Methods
From January 2012 to December 2018, a consecutive series of patients with BR or LAC PDAC was enrolled in a prospective cohort study after multidisciplinary discussion. Patients were stratified in four groups according to their elegibility and response to NAT: 1)resected patients, 2)patients who underwent explorative surgery after NAT but were not deemed resectable, 3)patients who did not respond to NAT and therefore not explored surgically and 4)patients not eligible for NAT due to poor performance status who received solely the best supportive care[BSC]. Overall survival (OS) and disease free survival (DSF) of the four different groups were analyzed. OS analysis was performed using the Kaplan-Meier method. Cox multivariate regression was performed to identify risk factors and predictors of survival.
Results
Fifty-five patients were enrolled in the study. The adopted chemotherapy regimens were mainly FFN and GEMPAC (51.06% and 36.17% respectively). Eight patients were not eligible for NAT due to poor general conditions. After NAT, 22 patients (41.81%) showed a biochemical/radiological response and were considered for surgery: 11 (47.82%) were radically resected with a DFS of 26.43 ± 5.51 months. Survivals related to the different groups were: 40.44 ± 4.27 months for resected patients, 19.82 ± 3.07 months for those explored but not resected, 14.29 ± 2.09 months for patients in progression and 5.66 ± 1.96 months for BSC patients. OS of BR patients resulted longer then LAC patients (25.08 ± 3.53 months vs 19.42 ± 2.76 months) but there was no statistically significant difference. Use of drugs other than FFN or GEMPAC was related to disease progression and poor overall survival (p <0.05). Lymph node involvement and increased Ca 19.9 after NAT where related to an higher risk of death (5.28 and 4.7 times respectively, p < 0.05).
Conclusions
NAT represents a key point in the treatment of BR and LAC PDAC. Response and downstaging rate after neoadjuvant therapy are variable and do not always translate into resectability. There is an urgent need of new RCTs to clarify the role of various therapeutic options and to identify subgroups of patients with different biological and genetic characteristics of PDAC.
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