Value of lymph node positivity in treatment planning for early stage pancreatic cancer

Background. Multimodal therapy is recommended for early stage pancreatic cancer, although whether all patients benefit and the optimal timing of chemotherapy remain unclear. Methods. Retrospective cohort study of patients aged 18-79 years with stage I-II pancreatic ductal adenocarcinoma in the National Cancer Database (2004-2012). Patients were grouped based on treatment strategy as surgery only, adjuvant, and preoperative. Accuracy of nodal staging and rate of nodal downstaging were ascertained using pretreatment clinical and postresection pathologic nodal status data. Association between overall risk of death and treatment strategy was evaluated with multivariable Cox regression. Results. Among 19,031 patients, 31.1 % underwent surgery only, 59.6% received adjuvant, and 9.3% preoperative therapy. Based on patients receiving upfront surgery, clinical nodal staging bore sensitivity, specificity, positive predictive value, and negative predictive value of 46.2%, 95.7%, 95.1 %, and 49.8%, respectively. Preoperative therapy downstaged 38% of cN1 patients to ypNO; 5-year overall survival for this group was 2 7.2% vs 12.3 % for ypN1 patients (P < .001). Relative to surgery only, adjuvant (HR 0.75, 95% CI [0.71-0.78]) and preoperative therapy (HR 0.66 [0.60-0.73]) were associated with lower risk of death among patients with pm, but not pNO (adjuvant HR 1.01 [0.94-1.09]; preoperative HR 1.10 [0.99-1.22]), disease. Conclusion. Our data provide strong support for preoperative chemotherapy for patients with node positive pancreatic cancer, one third of whom may be downstaged. Among those with seemingly node negative disease, half will be understaged with current clinical staging modalities. These results should be considered when planning treatment for patients with early stage pancreatic cancer.