Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial

Eva Versteijne*, Jacob L van Dam, Mustafa Suker, Quisette P Janssen, 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 V Homs, Jeanin E van Hooft, Emile D KerverSaskia A C Luelmo, Karen J Neelis, Joost 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, Geertjan van Tienhoven, Casper H J van Eijck, Dutch Pancreatic Cancer Group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported.

METHODS: In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial.

RESULTS: Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer.

CONCLUSION: Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.

Original languageEnglish
Pages (from-to)1220-1230
Number of pages15
JournalJournal of Clinical Oncology
Volume40
Issue number11
Early online date27 Jan 2022
DOIs
Publication statusPublished - 10 Apr 2022

Keywords

  • ADENOCARCINOMA
  • ADJUVANT CHEMOTHERAPY
  • CHEMORADIATION
  • GEMCITABINE
  • MULTICENTER
  • OPEN-LABEL
  • THERAPY
  • TRENDS

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