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Puckett et al. J Cancer Metastasis Treat 2020;6:11 I http://dx.doi.org/10.20517/2394-4722.2020.98 Page 3 of 8

disease in select patients may be associated with a possible prolonged and have served to encourage other
investigators to consider surgical removal of oligometastatic disease.

Metastatic PDAC most commonly involves the liver, followed by inter-aortocaval lymph nodes (ILN), lung,
and peritoneum [7,12] . However, distant metastasis in patients with PDAC has been documented in almost
every organ based on autopsy studies [13-19] . Surgical resection of liver and lung oligometastases with negative
margins can be technically feasible depending on the anatomic location; however, decisions regarding
oligometastasectomy should be based on predictions about tumor biology and careful patient selection.
Surgical resection of liver metastases may be safely accomplished at the time of pancreatic resection in select
patients, while pulmonary metastases can often be performed in a minimally invasive fashion after primary
pancreatic resection. In general, resection of oligometastatic PDAC lesions should be done in a staged
fashion after systemic chemotherapy that has demonstrated stable or responsive disease.

We herein performed a literature review of studies investigating whether there is a role for surgical resection
with curative intent of limited PDAC metastases to the lung or liver. The focus of this literature review was
on pulmonary and hepatic metastases given that the majority of available literature on oligometastasectomy
in PDAC is focused primarily on those two organs.

HEPATIC METASTASECTOMY
The liver is the most common location of PDAC metastases due to the proximity of the liver and blood
supply to the pancreas [20,21] . Approximately 70% of patients with metastatic PDAC have disease in the liver.
[22]
Among these patients, 30% have limited disease . While resection of colorectal liver metastasis is safe and
provides a survival benefit, the resection of liver metastases in non-colorectal patients, including pancreatic
[22]
cancer patients, has not been widely accepted . Because national guidelines do not recommend resection
[23]
of a primary tumor along with synchronous liver metastases, research on the topic is lacking . The general
treatment approach to liver metastases in PDAC is systemic chemotherapy and/or radiation therapy . In
[24]
addition, locoregional ablative techniques such as percutaneous radiofrequency ablation and microwave
ablation have been recognized as safe and less invasive alternatives to surgery with comparable recurrence
and survival outcomes [25-27] .

[9]
In a study by Hackert et al. , a total of 128 patients underwent surgery for oligometastatic PDAC with
spread to either the liver (85 patients) or ILN (43 patients) [Table 1]. Among these patients, 20 had received
neoadjuvant treatment. The patients underwent a variety of procedures including pancreaticoduodenectomy,
distal pancreatectomy, total pancreatectomy with splenectomy, extended lymphadenectomy,
bisegmentectomy, right hepatectomy, segmental liver resection ranging from 1-4 segments, and extended
right hepatectomy. Overall, 72.9% of the liver resections were performed at the time of primary pancreatic
resection with the rest performed following pancreatic resection at an average of 18.4 months later. The
majority of the liver metastases resected were less than 2 cm in diameter, and 96.4% of patients had more than
three metastatic lesions in the liver. Twenty patients had undergone neoadjuvant treatment prior to resection;
data on adjuvant therapy was only available for 95 patients, 73 of whom completed adjuvant therapy. Surgical
morbidity and 30-day mortality rates were 45.0% and 2.9% for the whole cohort, respectively. Median overall
survival was 12.3 months with a 5-year overall survival of 8.1% after liver resection and 10.1% after ILN
resection. There was no survival difference detected between patients that received neoadjuvant treatment
and those that did not. The number of liver metastases, size of liver metastases, and pre-operative CA 19-9
levels were not significantly associated with survival. There was also no significant difference in overall
survival between synchronously and metachronously resected patients when survival was analyzed from
time of liver resection.

[28]
A multi-institutional European study performed by Tachezy et al. examined a total of 69 patients with
PDAC and synchronous liver metastases who underwent combined pancreas and liver resections compared