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Lo et al. J Cancer Metastasis Treat 2022;8:30 Journal of Cancer
DOI: 10.20517/2394-4722.2022.48
Metastasis and Treatment

Review Open Access

The role of systemic therapy in borderline resectable
and locally advanced pancreatic ductal

adenocarcinoma

Victor C. K. Lo, Rachel A. Goodwin, Michael M. Vickers
Department of Medicine, Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada.

Correspondence to: Dr. Michael M. Vickers, Department of Medicine, Division of Medical Oncology, The Ottawa Hospital
Cancer Centre, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada. E-mail: mvickers@toh.ca

How to cite this article: Lo VCK, Goodwin RA, Vickers MM. The role of systemic therapy in borderline resectable and locally
advanced pancreatic ductal adenocarcinoma. J Cancer Metastasis Treat 2022;8:30. https://dx.doi.org/10.20517/2394-
4722.2022.48
Received: 10 May 2022 First Decision: 21 Jun 2022 Revised: 15 Jul 2022 Accepted: 4 Aug 2022 Published: 15 Aug 2022

Academic Editors: Marco Falasca, Palanisamy Nallasamy Copy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease, even in patients whose cancer is localized
and non-metastatic. Surgical resection provides the only option for cure, but long-term survival rates remain
dismal. For patients with borderline resectable (BR) disease who undergo upfront resection, many patients are
either too unwell for subsequent adjuvant systemic therapy, develop recurrence soon after, or are found to have
unresectable disease intra-operatively. There is increasing evidence for a neoadjuvant approach, using more
conventional multi-agent chemotherapy regimens, which have demonstrated higher activity in the metastatic
setting compared to single agents. For patients with locally advanced (LA) disease, which is unresectable by
current definitions, there is mounting evidence that effective neoadjuvant systemic therapy is able to convert some
patients’ disease to a resectable state, offering the potential for long-term survival and cure. Herein we present a
review of key trials focusing on prospective, randomized studies to provide high-level evidence supporting a
neoadjuvant approach to both BR and LA PDAC. However, many knowledge gaps exist, such as the optimal
neoadjuvant multi-agent chemotherapy regimen, the role of radiotherapy, and the safety and efficacy of adding
immunotherapy to chemo/radiation therapy. Future challenges in determining the optimal approach to patients
with BR or LA PDAC include not only overcoming the inherent difficulties in conducting complex, multidisciplinary,
multicentre randomized trials in patients with a high-morbidity and mortality disease, but also trying to standardize
disease definitions, treatment regimens, and outcome measures.

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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