To the Editor In the article by Jones et al,1 the authors conclude that pancreatic ductal adenocarcinoma behaves as a systemic disease, requiring more effective systemic therapies. While we agree that systemic therapy is critical, we feel that several points need to be made about the risk of local recurrence and the important role of local therapy.
First, the observed rate of local-only first failure in approximately 50% of patients warrants considerable thought because this rate is exceedingly high compared with other solid tumors in which extirpative surgery plays a major role. Given that the ability of an isolated local recurrence to potentially seed distant sites is a tangible risk, future efforts to further improve local control are certainly warranted. Second, local recurrence occurred at a median of 2.3 months later than the median time to distant recurrence, but the median survival rates associated with local-only and distant-only first recurrences were very similar. Furthermore, there were no differences in median survival measured from the time of recurrence between patients with local vs distant recurrences. Perhaps even more thought-provoking is that gemcitabine plus capecitabine led to fewer local-only first recurrences, while distant-only recurrences were higher. Finally, multivariate analysis found that positive resection margin and local invasion were significantly associated with poor survival and that local recurrence also trended to being significantly associated with worse survival (P = .054). Taken together, these findings argue that having a local-only first failure phenotype may be at least as poor a prognostic sign as having a metastatic-only first recurrence phenotype, and that lower rates of local recurrence observed in the experimental arm could be driving the observed survival improvement.
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Williams TM, Crane C, Goodman K. Recurrence After Resection of Pancreatic Ductal Adenocarcinoma. JAMA Surg. Published online January 02, 2020. doi:10.1001/jamasurg.2019.5464
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