A Single Center Experience in Resectable Pancreatic Ductal Adenocarcinoma : The Limitations of the Surgery-First Approach. Critical Review of the Literature and Proposals for Practice Update

Acta Gastroenterol Belg. Oct-Dec 2017;80(4):451-461.

Abstract

Background and study aims: The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature.

Patients methods: We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups.

Results: For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively.

Conclusions: Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.

Keywords: Belgium; neo-adjuvant therapy; outcome; pancreatic ductal adenocarcinoma; prognostic factors; surgery; vascular resection.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery*
  • Belgium / epidemiology
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / surgery*
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Humans
  • Neoplasm Recurrence, Local
  • Pancreatectomy / methods*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery*
  • Prognosis
  • Survival Rate