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Table 2. NCCN (Version 1.2022) definition of borderline resectable pancreatic adenocarcinoma
Arterial Venous
Pancreatic head/uncinate process: • Solid tumor contact with the SMV or PV of > 180°, contact of ≤ 180°
• Solid tumor contact with CHA without extension to CA or hepatic artery with contour irregularity of the vein or thrombosis of the vein but with
bifurcation allowing for safe and complete resection and reconstruction suitable vessel proximal and distal to the site of involvement allowing
• Solid tumor contact with the SMA of ≤ 180° for safe and complete resection and vein reconstruction.
• Solid tumor contact with variant arterial anatomy (ex. accessory right • Solid tumor contact with the IVC
hepatic artery, replaced right hepatic artery, replaced CHA, and the origin
of replaced or accessory artery) and the presence and degree of tumor
contact should be noted if present, as it may affect surgical planning
Pancreatic body/tail:
• Solid tumor contact with the CA of ≤ 180°
CHA: Common hepatic artery; CA: celiac axis; SMA: superior mesenteric artery; SMV: superior mesenteric vein; PV: portal vein; IVC: inferior vena
cava.

Notably, since the NCCN definitions, a number of other groups have developed similar but slightly different
definitions, such as the Americas Hepatopancreaticobiliary Association/ Society of Surgical
Oncology/Society for Surgery of the Alimentary Tract (AHPBA/SSO/SSAT) , MD Anderson Cancer
[23]
Centre , and Intergroup Alliance . In 2016 an international consensus was developed during the 20th
[24]
[25]
[26]
meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, and published in 2017 .
This definition includes not only the same anatomic considerations as above (and specifying borderline
resectable status by arterial or venous criteria), but also biological and conditional criteria. Specifically, if
there are suspicious findings for extra-pancreatic disease or a CA19-9 > 500 units/mL, and if the patient’s
Eastern Cooperative Group (ECOG) performance status was 2 or greater, patients would be considered to
have BR-PDAC. The International Study Group of Pancreatic Surgery (ISGPS) also published a consensus
statement for BR-PDAC in 2014 . They support the 2013 NCCN imaging-based criteria for borderline
[27]
resectability by using a specialized pancreatic CT protocol that includes the abdomen and pelvis, and that all
cases should be discussed and managed by a multi-disciplinary team. Nonetheless, there still exists variation
in the way that clinical trials have defined BR-PDAC when enrolling patients, and thus it remains critical to
scrutinize the definition used when comparing studies and drawing conclusions from BR-PDAC trials.

Systemic therapy in BR-PDAC
In the early 2010s, multi-agent chemotherapy was demonstrated to have improved overall survival (OS)
over gemcitabine alone in metastatic pancreatic adenocarcinoma, with regimens such as gemcitabine plus
nab-paclitaxel (GnP) and FFX [Table 3]. Following this, multi-agent regimens started to be used
[28]
[29]
neoadjuvantly for BR-PDAC in the absence of randomized data. A patient-level meta-analysis of
neoadjuvant FFX systemic therapy (median 4-9 cycles given) for BR-PDAC was published in 2019 and
found a median OS (mOS) of 22.2 months and a median progression-free survival (mPFS) of 18 months .
[30]
It analyzed data from 24 studies (313 patients), comprising 16 retrospective and 8 prospective studies of
phase I-II trials and cohort studies, mostly reporting intention-to-treat (ITT) analyses. ITT analysis is
critical as there are a significant number of enrolled patients who never received resection due to disease
progression or unresectable disease at the time of surgery, and excluding these patients would lead to
overestimates of OS. The resection rate was 67.8% with an R0 rate of 83.9%. The most common grade 3
adverse events (AEs) included: neutropenia (17.5%), diarrhea (11.1%), and fatigue (10.8%), with no deaths
attributable to FFX. Most notably, there were no randomized control trials (RCTs) in this meta-analysis,
and there was heterogeneity in the studies including variations in the FFX regimen, number of cycles
administered, use of chemoradiation, and borderline resectability criteria as described above. Nonetheless,
the body of evidence thus far suggests that neoadjuvant FFX has the potential to improve resection rates, R0
rates, and ultimately OS for patients with BR-PDAC.