RFA Open as Upfront Treatment for Locally Advanced Pancreatic Cancer: Requiem from a Randomized Controlled Trial

Purpose: Pancreatic adenocarcinoma has a dismal prognosis. Many efforts were directed towards new strategies to treat patients not eligible for radical surgery: local ablation may represent an option for LAPC management but no evidence supports its application. Aim of the study was to compare OS and PFS in patients receiving RFA plus conventional therapy (CHT-RT) with patients receiving only conventional treatment. Methods: This is a multicentric prospective randomized trial.Patients with a new diagnosis of LAPC observed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA(A) or standard CHT-RT(B).Morbidity,CHT-RT details,recurrence,PFS and OS were recorded.Survival analyses used the Kaplan-Meier method.Data were statistically significant for p< 0.05. Results: One hundred patients were enrolled from January 2014 to August 2016 with a more frequent combined infiltration of both the artero-venous peripancreatic axis (47%); 33% of patients in Group A didn't received the designated procedure because of i.o. finding of liver(18.7%),peritoneal metastases(43.8%)or technical contraindications(37.5%). In 23 cases (47.9%), an associated surgical procedure was performed. Mortality was zero and RFA-related morbidity was 15.6%.Among Group B, 74.3% received Gem-NabPaclitaxel and 25.7%other Gem based therapy. In 13 cases(13%), conversion to surgery occurred(2 RFA and 11 CHTRT).The mean OS was 21.1 months(17.7-24.6).No survival benefit from RFA was observed if compared to CHTRT (19.4 months and 22.1 months respectively,p=0.639).Mean overall PFS was 10.3 months with no advantage in the RFA arm with PFS of 11.1 months vs. 9.6 months after CHRT,p=0.570. Conclusion: This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC: despite RFA alone does not give any advantage in terms of OS or PFS compared to CHTRT, it could be considered an option only within a multidisciplinary context and after neoadjuvant therapies, with a mininvasive approach. We believe that pursuing new therapeutic paths to provide more than 14-16 months of overall survival to advanced non-metastatic patients was our commitment at the time we conceived this study, and still is.