In the Dutch phase III PREOPANC trial reported in the Journal of Clinical Oncology, Versteijne et al found that preoperative chemoradiotherapy did not improve overall survival vs immediate surgery in patients with resectable and borderline resectable pancreatic cancer. Benefits of preoperative treatment were observed in secondary endpoint and subgroup analyses, though additional evidence is required to clarify those findings.

Study Details

In the multicenter trial, 246 patients were randomly assigned to preoperative chemoradiation followed by surgery (n = 119) or immediate surgery (n = 127), both followed by six courses of adjuvant gemcitabine at 1,000 mg/m² on days 1, 8, and 15 over 4 weeks. Chemoradiation consisted of 15 fractions of radiotherapy at 2.4 Gy over 3 weeks combined with 1,000 mg/m² of gemcitabine on days 1, 8, and 15 over 4 weeks, with one cycle of gemcitabine at 1,000 mg/m² on days 1 and 8 over 3 weeks given before and after the concurrent cycle.

The primary endpoint was overall survival on intention-to-treat analysis.

Overall Survival

Median follow-up was 27 months. Median overall survival was 16.0 months in the preoperative chemoradiotherapy group and 14.3 months in the immediate surgery group on intent-to-treat analysis (hazard ratio [HR] = 0.78, P = .096). The resection rate was 61% vs 72% (P = .058), and the R0 resection rate among those undergoing resection was 71% vs 40% (P < .001).

Preoperative chemoradiotherapy was associated with significantly improved disease-free survival (HR = 0.73, P = .032) and locoregional failure-free interval (HR = 0.56, P = .0034).  With preoperative chemoradiotherapy, fewer patients had pathologic lymph nodes, perineural invasion, and venous invasion.

Among 55 patients in the preoperative chemoradiotherapy group and 65 in the immediate surgery group constituting the predefined subgroup of patients with tumor resection who started adjuvant treatment, median overall survival was 35.2 months vs 19.8 months (HR = 0.58, P = .029). In this subgroup, preoperative chemoradiotherapy was also associated with significantly improved disease-free survival, locoregional failure-free interval, and distant metastasis-free interval.

Adverse Events

Serious adverse events occurred in 52% of the preoperative chemoradiation group vs 41% of the immediate surgery group (P = .096). Death due to serious adverse events occurred in eight patients in each group, including three patients in each group with postoperative mortality. Among patients undergoing resection, postoperative complications occurred in 49 (68%) of 72 patients in the preoperative chemoradiotherapy group vs 46 (50%) of 92 patients in the immediate surgery group (P = .026).

The investigators concluded, “Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary endpoints and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.”

Geertjan van Tienhoven, MD, PhD, of the Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, is the corresponding author for the Journal of Clinical Oncology article.

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