Background: Since randomized controlled trials have indicated that adjuvant chemotherapy prolongs survival and reduces recurrence rates after surgical resection of pancreatic adenocarcinoma, a gemcitabine based chemotherapy has become part of the interdisciplinary treatment concept for pancreatic cancer in accordance to current guidelines.
Objectives: The aim of this project was to analyse the validity of the CONKO-001 trial as a basis for the recommendation of adjuvant chemotherapy in many international guidelines.
Methods: We analysed the validity of the CONKO-001 trial regarding study design, recruitment period, participating institutions, patient selection, randomisation, stratification, standardization of surgical treatment and histological examination, statistical methods and interpretation of results. We additionally analysed the study regarding the risk of bias using the RoB 2 Tool. Finally we reviewed the influence of the pharmaceutical industry and potential conflicts of interest.
Results: We identified several shortcomings of the study concerning the study protocol, the participating clinics, the patient recruitment, the randomization pattern, the standardization of surgical treatment and histological examination, the statistical methods, the evaluation of the results and the influence of the pharmaceutical industry. According to the Cochrane RoB 2 Tool the study was judged to raise some concerns in three of the five risk domains for the outcome "overall survival".
Conclusions: Based on our review, the results of the CONKO-001-study should be revisited and critically reviewed. The recommendation to include adjuvant chemotherapy with gemcitabine deserves a critical appraisal.
Keywords: Pancreatic cancer; adenocarcinoma; adjuvant chemotherapy; guidelines recommendation; randomized controlled trials; validity.