When considering the most favorable patients with PAC the outcomes should be excellent, unfortunately they remain dismal. Currently, the role of radiation therapy is controversial in patients with resectable PAC due to the lack of definitive data evaluating the use of adjuvant therapy using modern radiotherapy techniques. The initial study evaluating adjuvant chemotherapy and radiation for PAC, the Gastrointestinal Tumor Study Group (GITSG) clinical trial, established adjuvant radiotherapy to be superior to observation in patients with resected PAC [
4]. The study was stopped early due to poor accrual (43 patients in 8 years). It showed, however, that the treated group experienced a survival benefit with longer median survival (21.0 months vs. 10.9 months;
p < 0.05) and 2-year survival (43% vs. 19%). This study was criticized for its small sample size and low radiation dose (40Gy split course) [
5]. Following the publication of the GITSG trial, the European Study Group for Pancreatic Cancer 1 (ESPAC-1) trial was conducted, this was a pivotal historic moment in the management of patients with PAC, particularly with regard to the role of radiation therapy. Notable is that this trial has been widely criticized, particularly with regard to the radiation therapy delivered [
6,
7]. In this multi-center, 2 × 2 factorial design, 73 patients with resected pancreatic adenocarcinoma were assigned to chemoradiation therapy alone, 75 patients to chemotherapy alone, 72 patients to both chemoradiation therapy and chemotherapy, and 69 patients to observation. Again, the critiques of this study abound, particularly with regard to the radiation therapy [
8]. The radiation delivered in this study was antiquated and a wide range of doses and techniques could have been employed. The critiques of the ESPAC-1 trial have been the subject of multiple editorials and a detailed review of these is beyond the scope of this article. In summary, it is well understood, by modern standards, that such radiation therapy doses and treatment strategies applied in either the GITSG trial or the ESPAC-1 are woefully inferior to contemporary radiation standards. The recommended radiation dose for the trial, 40 Gy delivered in a split course fashion with a break between the delivery of the first and second half of treatment, is clearly a biologically ineffective dose and delivery method. In fact, the split course has been shown to be inferior in many other cancer types, and may actually allow for accelerated repopulation of tumor cells that could lead to worse outcomes [
9‐
11]. Judgements regarding the use of radiation therapy for patients with resectable pancreatic adenocarcinoma based on the ESPAC-1 trial should be made with extreme caution. Nevertheless, the publication of the ESPAC-1 trial has led to subsequent omission of radiation therapy from most European adjuvant trials, including ESPAC-3 [
12] and ESPAC-4 [
13]. In North America, radiation therapy has remained part of the adjuvant treatment strategy, and several trials have been presented since then, including RTOG 9704, however none have examined, in a randomized fashion, the role of modern era radiation therapy [
14]. The successor trial to RTOG 9704, RTOG 0848, will help to answer the question regarding the role of adjuvant chemo-RT. RTOG 0848 has completed enrollment and results are anticipated in the coming years. Although the RTOG 0848 addresses the adjuvant radiotherapy question, the recent publication of the PRODIGE trial which demonstrated a significant benefit for adjuvant FOLFIRINOX over gemcitabine alone, has established FOLFIRINOX as the standard of care for adjuvant chemotherapy. Thus, the impact of adjuvant chemoradiation after gemcitabine-based chemotherapy may be less relevant. Nonetheless, local failure rates were still high on the PRODIGE study with a component of local/regional present in over 20% of cases [
23]. To date the question as to the role of post-operative radiation in PAC, as addressed in a phase III trial, using modern era RT with robust quality assurance, remains unanswered.