What clinical factors are associated with a major pathologic response following preoperative therapy for pancreatic ductal adenocarcinoma?
In this study of 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who were treated with preoperative therapy, those with a pathologic complete response or less than 5% viable cancer cells had a significantly longer median survival duration (73.4 months vs 32.2 months). On multivariable logistic regression analysis, young age, low baseline cancer antigen 19-9 level, and the use of gemcitabine as a radiosensitizer were associated with a major pathologic response.
The patient, treatment, and tumor-related factors identified in this study may define a group of patients most likely to experience a significant response to preoperative therapy.
We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined.
To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma.
Design, Setting, and Participants
Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015.
Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%).
Main Outcomes and Measures
Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression.
Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P < .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009).
Conclusions and Relevance
Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.
Cloyd JM, Wang H, Egger ME, Tzeng CD, Prakash LR, Maitra A, Varadhachary GR, Shroff R, Javle M, Fogelman D, Wolff RA, Overman MJ, Koay EJ, Das P, Herman JM, Kim MP, Vauthey J, Aloia TA, Fleming JB, Lee JE, Katz MHG. Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma. JAMA Surg. Published online July 12, 2017. doi:10.1001/jamasurg.2017.2227