As reported in the Journal of Clinical Oncology by Versteijne et al, long-term follow-up of the Dutch phase III PREOPANC trial has shown an overall survival benefit among patients receiving neoadjuvant chemoradiotherapy vs upfront surgery for resectable and borderline resectable pancreatic cancer; estimated survival rates at 5 years were 20.5% vs 6.5%. Initial results from the trial, previously reported, showed no significant difference in overall survival at a median follow-up of 27 months.

Study Details

In the multicenter trial, 246 eligible patients were randomly assigned between April 2013 and July 2017 to receive neoadjuvant chemoradiotherapy (n = 119; 54 with borderline resectable disease) or upfront surgery (n = 127; 59 with borderline resectable disease). Patients in the neoadjuvant group received three cycles of gemcitabine with radiotherapy at 36 Gy in 15 fractions during the second cycle; patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome measure was overall survival in the intention-to-treat population.  

Key Findings

After a median follow-up of 59 months, 93 patients in the neoadjuvant group (78%) vs 117 in the upfront surgery group (92%) had died. Median overall survival was 15.7 months (95% confidence interval [CI] = 12.9–20.6 months) in the neoadjuvant group vs 14.3 months (95% CI = 12.7–17.9 months) in the upfront surgery group (hazard ratio [HR] = 0.73, 95% CI = 0.56–0.96, P = .025).

Overall survival estimates were 27.7% (95% CI = 20.7%–37.1%) vs 16.5% (95% CI = 11.1%–24.4%) at 3 years and 20.5% (95% CI = 14.2%–29.8%) vs 6.5% (95% CI = 3.1%–13.7%) at 5 years.

Hazard ratios for overall survival in the neoadjuvant group vs upfront surgery group were 0.79 (95% CI = 0.54–1.16, P = .23) among patients with resectable disease and 0.67 (95% CI = 0.45–0.99, P = .045) among those with borderline resectable disease. Hazard ratios favored the neoadjuvant group for disease-free survival (0.69, 95% CI = 0.53–0.91, P = .009), locoregional failure–free interval (0.57, 95% CI = 0.39–0.83, P = .004), and distant metastases–free interval (0.74, 95% CI = 0.54–1.03, P = .070).

Palliative chemotherapy for disease progression or recurrence was initiated in 35 (40%) of 84 patients (40%) in the neoadjuvant group and in 36 (33%) of 108 in the upfront surgery group (P = .37).

The investigators concluded, “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.”

Eva Versteijne, MD, PhD, of the Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Dutch Cancer Foundation. For full disclosures of the study authors, visit ascopubs.org.