Preoperative Chemotherapy for Pancreatic Cancer Improves Survival and R0 Rate Even in Early Stage I

Background While preoperative chemotherapy for patients with stage II-III pancreatic adenocarcinoma (PDAC) is frequently practiced, its impact on very early PDAC (stage I) remains unclear today. Material and Methods Patients undergoing pancreatectomy for PDAC between 2010 and 2016 were identified in the National Cancer Database. Early-stage patients (IA-IB) with complete oncologic and clinical information and more than 30-day survival were included. The effect of preoperative chemotherapy on margin status was assessed with binary logistic regression. Following correction for confounders, the effect of therapy sequencing was assessed via comparison of preoperative, postoperative, perioperative (pre- and post-operative) chemotherapy, and surgery only using Cox regression. Results Of 4785 patients, 688 (14.4%) were stage IA, and 4197 (87.7%) IB. The rate of preoperative chemotherapy was only 8.8%. Rate of margin positivity was lower for preoperative chemotherapy (12.3% vs 19.7%). After correcting for confounders, the risk of a positive margin was lower in preoperative chemotherapy (odd ratio [OR] 0.703, p = 0.042). Cox regression showed a significant overall survival advantage for preoperative (hazard ratio [HR] 0.784, p = 0.002), postoperative (HR 0.618, p < 0.001), and perioperative (HR 0.601, p < 0.001) chemotherapy compared with surgery alone. There was no significant difference in survival between chemotherapy groups but a trend towards optimal survival for preoperative chemotherapy. Conclusion Despite preoperative chemotherapy vs surgery alone resulting in improved R0 rates and overall survival even in stage I PDAC, it is rarely practiced. The results presented here suggest that preoperative chemotherapy should be strongly considered in all patients with resectable PDAC, including very early PDAC.