Editorial About: “A Prospective, Open-Label, Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma”

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that affected approximately 53,000 new patients in 2016. Patients with a diagnosis of this malignancy have a 5-year overall survival rate of 10%, which increases only to 25% for those with resectable disease. These poor outcomes reflect two notions. First, PDAC is a systemic disease at the time of diagnosis regardless of clinical stage. As such, treatment must include systemic therapy as one component of the therapy. Second, despite progressive advances during the last several years, current treatment options have limited efficacy at reducing recurrences and disease progression. Historically, results from studies evaluating the use of radiotherapy for PDAC have been mixed, with adjuvant radiotherapy trials showing disparate results. The report entitled ‘‘A Prospective, Open-Label Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent With Radiation for Resectable Pancreatic Ductal Adenocarcinoma’’ described the role of neoadjuvant radiation (total dose, 50.4 Gy) given concurrently with full doses of chemotherapy (gemcitabine and S1). The authors demonstrated an impressive median survival of 55 months for 63 patients who had resectable and borderline resectable tumors treated with this regimen. This trial adds to the body of knowledge regarding the use of neoadjuvant chemoradiation in the treatment of pancreatic cancer. The unique aspect of this trial was full doses of chemotherapy delivered concurrently with radiation, thus targeting both local and distant disease. The results of this study should be taken in light of other recent trials. The PREOPANC-1 trial was a phase 3 trial that evaluated the role of preoperative chemoradiotherapy versus immediate surgery for 246 patients with resectable or borderline resectable tumors. All the patients received 6 months of perioperative gemcitabine. Despite equal total doses of systemic chemotherapy, the trial demonstrated improvements in both median recurrencefree survival [median, 9.9 vs 7.7 months; hazard ratio (HR), 0.67; p = 0.010] and overall survival (median, 17.1 vs 13.5 months; HR, 0.71; p = 0.047) with the neoadjuvant chemoradiation approach. It is important to note that the patients in the chemoradiation arm of the study received 30% of all the systemic chemotherapy during the preoperative period. Moreover, this trial did not use the more active systemic regimens available currently. The randomized phase 2 and 3 Prep-02/JSAP-05 trial, which used the same chemotherapy regimen in the experimental arm as the current study used, compared the use of neoadjuvant chemotherapy with the use of upfront surgery followed by adjuvant S-1 chemotherapy. The study demonstrated a significantly improved median overall survival of 36.7 months in the neoadjuvant therapy cohort versus 26.7 months in the upfront surgery cohort (p = 0.015), with a 2-year overall survival rate of 64% versus 53%. Therefore, the single-arm design of the current study begs the question regarding the individual Society of Surgical Oncology 2019