Postoperative Chemotherapy Benefits Patients Who Received Preoperative Therapy and Pancreatectomy for Pancreatic Adenocarcinoma

Supplemental Digital Content is available in the text Objective: We sought to determine whether postoperative chemotherapy after preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) prolongs survival. Background: Data to support administering postoperative chemotherapy to patients who received preoperative therapy are lacking. Methods: All patients with PDAC who underwent pancreatectomy after preoperative therapy between 2010 and July 2017 at The University of Texas MD Anderson Cancer Center were identified. To control for selection bias, patients who received postoperative therapy and patients who did not were matched by propensity scores based on factors associated with the use of postoperative chemotherapy. Results: Among 245 patients treated with a median of 4 cycles of preoperative treatment and pancreatectomy, 155 (63%) initiated postoperative chemotherapy and 90 (37%) did not. Patients who received postoperative therapy had a higher median cancer antigen 19-9 level before surgery, larger median tumor diameter, higher rate of extrapancreatic invasion, and lower rate of pathologic major response. The propensity-matched cohort comprised 122 patients: 61 who received postoperative chemotherapy and 61 who did not. The median overall survival (OS) and recurrence free survival (RFS) for patients who received postoperative therapy were 42 and 17 months, respectively, versus 32 and 12 months for patients who did not (OS: P = 0.06; RFS: P = 0.04). Postoperative therapy was marginally associated with a longer OS (hazard ratio 0.55, 95% confidence interval 0.29–1.01; P = 0.05) and significantly associated with a longer RFS (hazard ratio 0.55, 95% confidence interval 0.29–0.96; P = 0.04). Conclusions: Despite being administered more frequently to patients with poor prognostic factors, postoperative chemotherapy after preoperative therapy and pancreatectomy for PDAC was of clinical benefit.

[1]  Distal Pancreatectomy , 2020, Definitions.

[2]  J. Cameron,et al.  Recurrence after neoadjuvant therapy and resection of borderline resectable and locally advanced pancreatic cancer. , 2019, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[3]  Jeffrey E. Lee,et al.  Radiographic and Serologic Predictors of Pathologic Major Response to Preoperative Therapy for Pancreatic Cancer. , 2019, Annals of surgery.

[4]  J. Berlin,et al.  Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  W. Harmsen,et al.  Factors Predicting Response, Perioperative Outcomes, and Survival Following Total Neoadjuvant Therapy for Borderline/Locally Advanced Pancreatic Cancer. , 2019, Annals of surgery.

[6]  Thierry Lecomte,et al.  FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer , 2018, The New England journal of medicine.

[7]  G. Stoddard,et al.  Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy , 2018, Journal of Gastrointestinal Surgery.

[8]  A. Zwinderman,et al.  Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial. , 2018, Journal of Clinical Oncology.

[9]  B. Erickson,et al.  Is Adjuvant Therapy Necessary for All Patients with Localized Pancreatic Cancer Who Have Received Neoadjuvant Therapy? , 2017, Journal of Gastrointestinal Surgery.

[10]  E. Nakakura,et al.  Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. , 2017, Journal of the National Comprehensive Cancer Network : JNCCN.

[11]  A. Vahrmeijer,et al.  Is Neoadjuvant Therapy Sufficient in Resected Pancreatic Cancer Patients? A National Study , 2017, Journal of Gastrointestinal Surgery.

[12]  P. Philip,et al.  SWOG S1505: A randomized phase II study of perioperative mFOLFIRINOX vs. gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinoma. , 2017 .

[13]  M. Büchler,et al.  Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial , 2017, The Lancet.

[14]  J. Berlin,et al.  Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Jeffrey E. Lee,et al.  Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival , 2016, The American journal of surgical pathology.

[16]  L. Schwartz,et al.  Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. , 2016, JAMA surgery.

[17]  A. Zwinderman,et al.  Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial , 2016, Trials.

[18]  Jeffrey E. Lee,et al.  Superior Mesenteric Artery Margin of Posttherapy Pancreaticoduodenectomy and Prognosis in Patients With Pancreatic Ductal Adenocarcinoma , 2015, The American journal of surgical pathology.

[19]  Jeffrey E. Lee,et al.  The Addition of Postoperative Chemotherapy is Associated with Improved Survival in Patients with Pancreatic Cancer Treated with Preoperative Therapy , 2015, Annals of Surgical Oncology.

[20]  Jeffrey E. Lee,et al.  Active Surveillance for Adverse Events Within 90 Days: The Standard for Reporting Surgical Outcomes After Pancreatectomy , 2015, Annals of Surgical Oncology.

[21]  P. Bhosale,et al.  Imaging of pancreatic neoplasms. , 2014, Surgical oncology clinics of North America.

[22]  A. Hinke,et al.  Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. , 2013, JAMA.

[23]  Jeffrey E. Lee,et al.  Yield of clinical and radiographic surveillance in patients with resected pancreatic adenocarcinoma following multimodal therapy. , 2012, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[24]  H. Friess,et al.  Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. , 2010, JAMA.

[25]  A. Renshaw,et al.  Protocol for the examination of specimens from patients with carcinoma of the penis. , 2010, Archives of pathology & laboratory medicine.

[26]  Douglas B. Evans,et al.  Development of an Integrated Biospecimen Bank and Multidisciplinary Clinical Database For Pancreatic Cancer , 2008, Annals of Surgical Oncology.

[27]  E. McFadden,et al.  Toxicity and response criteria of the Eastern Cooperative Oncology Group , 1982, American journal of clinical oncology.

[28]  Jeffrey E. Lee,et al.  Treatment Sequencing for Resectable Pancreatic Cancer: Influence of Early Metastases and Surgical Complications on Multimodality Therapy Completion and Survival , 2013, Journal of Gastrointestinal Surgery.

[29]  T. Eberlein Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer: A Randomized Controlled Trial , 2008 .