Pancreas
J Clin Oncol. 2022;40(11):1220–30
Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: Long-term results of the Dutch randomized PREOPANC trial
Purpose: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported.
Methods: In this multicenter, phase 3 trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of 3 cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by 4 cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by 6 cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial.
Results: Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio = 0.73; 95% confidence interval [CI]: 0.56–0.96; p = 0.025). Although the difference in median survival was only 1.4 months (15.7 vs. 14.3 months), the 5-year OS rate was 20.5% (95% CI: 14.2–29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI: 3.1–13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer.
Conclusion: Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves overall survival compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.