Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the Dutch randomized PREOPANC trial
Open accessAbstract
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.
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Self-citation
- Authors
- Versteijne, E., van Dam, J. L., Suker, M., Janssen, Q. P., Groothuis, K., Akkermans-Vogelaar, J. M., Besselink, M. G., Bonsing, B. A., Buijsen, J., Busch, O. R., Creemers, G.-J. M., van Dam, R. M., Eskens, F. A. L. M., Festen, S., de Groot, J. W. B., Groot Koerkamp, B., de Hingh, I. H., Homs, M. Y. V., van Hooft, J. E., Kerver, E. D., Luelmo, S. A. C., Neelis, K. J., Nuyttens, J., Paardekooper, G. M. R. M., Patijn, G. A., van der Sangen, M. J. C., de Vos-Geelen, J., Wilmink, J. W., Zwinderman, A. H., Punt, C. J., van Tienhoven, G., van Eijck, C. H. J., & for the Dutch Pancreatic Cancer Group
- Affiliations
- Amsterdam University Medical Centers (NL)
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
- Erasmus MC Cancer Institute (NL)
- Netherlands Comprehensive Cancer Organisation (NL)
- Leiden University Medical Center (NL)
- Maastricht University Medical Centre (NL)
- Catharina Ziekenhuis (NL)
- Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
- OLVG (NL)
- Department of Medical Oncology, Isala Oncology Center, Zwolle, the Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Isala (NL)
- Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands
- Department of Internal Medicine, Division of Medical Oncology, GROW—School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, the Netherlands
- Amsterdam UMC Location University of Amsterdam (NL)
- Utrecht University (NL)
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- ORCID
- Versteijne, Eva
- van Dam, Jacob L.
- Suker, Mustafa
- Akkermans-Vogelaar, Janine M.
- Besselink, Marc G.
- Bonsing, Bert A.
- Buijsen, Jeroen
- Busch, Olivier R.
- Creemers, Geert-Jan M.
- van Dam, Ronald M.
- Festen, Sebastiaan
- Groot Koerkamp, Bas
- van Hooft, Jeanin E.
- Luelmo, Saskia A. C.
- van der Sangen, Maurice J. C.
- de Vos-Geelen, Judith
- Wilmink, Johanna W.
- Zwinderman, Aeilko H.
- Punt, Cornelis J.
- Venue
- Journal of Clinical Oncology
- Published
- 2022-04-10
- Volume
- 40
- Issue
- 11
- Pages
- 1220-1230
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W4210426142
- Cited by
- 786
- References
- 29
- Citations by year
- 2026: 147 · 2025: 175 · 2024: 184 · 2023: 184 · 2022: 95
- FWCI
- 67.13
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- Abbott Laboratories
- Amgen
- Pfizer
- AstraZeneca
- Les Laboratories Pierre Fabre
- Eisai
- Servier
- Ipsen
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- pancreatic cancer, neoadjuvant chemoradiotherapy, upfront surgery, borderline resectable pancreatic cancer, resectable pancreatic cancer, gemcitabine, radiotherapy, adjuvant gemcitabine, overall survival, long-term outcomes, subgroup analysis, prognostic factors, treatment toxicity, quality of life
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Humans, Pancreatic Neoplasms, Survival Rate, Neoadjuvant Therapy, Chemoradiotherapy
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