Nodal downstaging as a treatment goal for node-positive pancreatic cancer

Nodal metastases portend a poor prognosis in patients with localized pancreatic cancer. Neoadjuvant therapy is associated with pathologic nodal downstaging in up to 38% of patients. However, the optimal type of neoadjuvant therapy for achieving nodal downstaging is unclear.

We conducted a retrospective cohort study of patients with nonmetastatic, clinically node-positive pancreatic cancer treated with neoadjuvant therapy and surgery identified in the National Cancer Database (2006-2014). Patients were stratified based on the neoadjuvant therapy regimens they received: multiagent chemotherapy; single-agent chemotherapy; multiagent chemotherapy with radiation; and single-agent chemotherapy with radiation. Associations between nodal downstaging and the type of neoadjuvant therapy received and overall risk of death were evaluated using multivariable regression analyses.

Among the 603 pancreatic ductal adenocarcinoma patients treated with neoadjuvant therapy, 400 received multiagent chemotherapy (202 with radiation) and 203 received single agent chemotherapy (151 with radiation). Relative to multiagent chemotherapy, single-agent chemotherapy was associated with a lower likelihood of nodal downstaging (relative risk ratio 0.38 [95% CI 0.17-0.85]). Use of radiation was associated with a significantly greater likelihood of nodal response (single-agent chemotherapy with radiation: relative risk ratio 1.77 [1.36-2.30]; multiagent chemotherapy with radiation: relative risk ratio 1.91 [1.49-2.45]; radiation use overall (versus no radiation): relative risk ratio 2.12 [1.68-2.68]). Compared with patients who remained pathologically node positive after neoadjuvant therapy, node negative status was associated with a significantly lower risk of death (hazard ratio 0.61 [0.49-0.76]) regardless of whether radiation was used (hazard ratio 0.63 [0.48-0.82]) or not (hazard ratio 0.45 [0.29-0.72]).

Nodal downstaging is associated with a survival benefit in patients with node-positive pancreatic ductal adenocarcinoma and is most likely to be achieved with neoadjuvant therapy that includes radiation. Single-agent chemotherapy neoadjuvant therapy was least likely to result in nodal downstaging.