Long-term results from the Dutch PREOPANC randomized, controlled trial confirm that
Neoadjuvant therapy remains controversial in this patient population, which makes up 15% of pancreatic cancer cases. Historically, these patients have been treated with surgery followed by adjuvant chemotherapy, but only about half of patients ever receive adjuvant chemotherapy due to early recurrence, surgical complication, or worsening disease. Neoadjuvant chemoradiotherapy is thought to increase the fraction of patients who receive chemotherapy. Improved exposure to chemotherapy could increase survival, and may also increase the rate of microscopically margin-negative resections.
Neoadjuvant chemoradiotherapy has become increasingly common, but the practice is based on retrospective analysis and small, phase II trials.
“This phase III, randomized trial demonstrates a long-term survival benefit with neoadjuvant treatment compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer,” the researchers wrote in the study, published online Jan. 27 in the Journal of Clinical Oncology. “The effect of neoadjuvant chemoradiotherapy was consistent across subgroups, including resectable and borderline resectable disease,” they added.
The new data represent long-term follow-up of 246 patients who had been randomized to neoadjuvant chemoradiotherapy or upfront surgery. Short-term data, published in 2020, showed trends toward improved survival but no statistically significant difference at a median of 27 months of follow-up. In the update, after a median follow-up of 59 months, patients in the neoadjuvant chemoradiotherapy group had better overall survival (hazard ratio [HR], 0.73; P = .025) and the 5-year overall survival was higher in the neoadjuvant chemoradiotherapy group (20.5%; 95% confidence interval [CI], 14.2%-29.8%) than the upfront surgery group (6.5%; 95% CI, 3.1%-13.7%).
Subgroup analyses found a survival advantage for upfront chemoradiotherapy among patients with borderline resectable tumors (HR, 0.67; P = .045), and a trend toward improved survival among patients with resectable tumors (HR, 0.79; P = .23). There was a trend toward more serious adverse events in the upfront chemoradiotherapy group (52% versus 41%; P = .096). There was no difference in major surgical complications or postoperative mortality.
The study found high progression rates within the first year in both the neoadjuvant chemoradiotherapy group and the upfront surgery group. “Apparently, our neoadjuvant schedule was not able to prevent many of these early progressions, and more effective schedules are warranted,” the authors wrote.
The survival outcomes were lower than those found in adjuvant trials, likely because of differences in patient populations. Adjuvant studies generally recruit patients who have recovered well from resection and have no early signs of recurrence, and therefore have a more favorable prognosis.
The long-term results from PREOPANC are in agreement with four previous studies that compared neoadjuvant chemoradiotherapy to upfront surgery.
A limitation of the study was that gemcitabine monotherapy was used in the adjuvant setting, and this regimen is now considered out of date.
The study was funded by the Dutch Cancer Foundation.