Background: Neoadjuvant therapy (NAT) has been increasingly employed to optimize outcomes in pancreatic cancer; however, little is known about its pathologic impact. Methods: The National Cancer Data Base (2003–2011) was retrospectively reviewed for patients with pancreatic carcinoma who underwent initial surgery or NAT followed by resection. Response to NAT, determined by comparing clinical and pathologic stage, and survival were evaluated. Results: 16,087 patients underwent initial pancreatectomy and 2307 patients received NAT. Clinical stage correlated poorly with pathological stage in patients who received initial surgery (κ = 0.2865, p < 0.001). With NAT, 21.9% were downstaged, 47.9% had no stage change, and 30.3% progressed. In clinical stage II disease, patients downstaged with neoadjuvant chemotherapy or multimodality therapy demonstrated improved survival over patients who did not respond or who progressed (P = 0.0022, P = 0.0012, respectively). This benefit was not preserved in stage III disease (P = 0.7380, P = 0.0726, respectively). In multivariable analysis, downstage in disease was associated with a 19% lower hazard of mortality (HR 0.81, 95% CI: 0.7–0.92, P = 0.002). Conclusions: Clinical stage correlates poorly with pathological stage in resectable pancreatic cancer. The majority of patients do not experience a change in stage with NAT. Those with early stage disease, responsive to NAT, experience a survival benefit.
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