Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial

Eva Versteijne, Mustafa Suker, Karin Groothuis, Janine M. Akkermans-Vogelaar, Marc G. Besselink, Bert A. Bonsing, Jeroen Buijsen, Olivier R. Busch, Geert-Jan M. Creemers, Ronald M. van Dam, Ferry A. L. M. Eskens, Sebastiaan Festen, Jan Willem B. de Groot, Bas Groot Koerkamp, Ignace H. de Hingh, Marjolein Y. Homs, Jeanin E. van Hooft, Emile D. Kerver, Saskia A. C. Luelmo, Karen J. NeelisJoost Nuyttens, Gabriel M. R. M. Paardekooper, Gijs A. Patijn, Maurice J. C. van der Sangen, Judith de Vos-Geelen, Johanna W. Wilmink, Aeilko H. Zwinderman, Cornelis J. Punt, Casper H. van Eijck, Geertjan van Tienhoven*, Dutch Pancreatic Canc Grp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

324 Citations (Web of Science)

Abstract

PURPOSE Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.

PATIENTS AND METHODS In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 x 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.

RESULTS Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P <.001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096).

CONCLUSION Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.

Original languageEnglish
Pages (from-to)1763-1773
Number of pages12
JournalJournal of Clinical Oncology
Volume38
Issue number16
DOIs
Publication statusPublished - 1 Jun 2020
Event54th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) - Chicago, United States
Duration: 1 Jun 20185 Jun 2018

Keywords

  • FULL-DOSE GEMCITABINE
  • NEOADJUVANT CHEMORADIATION
  • ADJUVANT CHEMOTHERAPY
  • DUCTAL ADENOCARCINOMA
  • CONCURRENT RADIATION
  • OPEN-LABEL
  • THERAPY
  • MULTICENTER
  • FOLFIRINOX
  • SURVIVAL

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