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

developed lung-only disease, survival was significantly longer (67.5 months) for patients who received
surgical resection or stereotactic radiosurgery (n = 8) compared to chemotherapy (33.8 months) or
observation (29.9 months).

[38]
Similarly, another study by Yamashita et al. identified 142 resected PDAC patients, 14 of whom developed
isolated pulmonary recurrence. Patients who had isolated pulmonary recurrence had significantly longer
survival than those with metastatic disease to other locations (40.3 vs. 20.9 months, P = 0.0156). The two
patients who underwent pulmonary metastasectomy survived for 70 months after resection.

Overall, a small amount of retrospective data shows improved survival for staged resection of isolated
pulmonary metastases in PDAC, especially if combined with adjuvant chemotherapy and/or radiation. The
data also suggests that lung-only metastatic disease may be more indolent than metastatic disease in other
locations making it a reasonable target for metastasectomy in select patients.

CONCLUSION
As recurrence and liver metastasis associated with resected pancreatic cancer is quite high and most systemic
regimens only improve survival by a few months, resection of oligometastatic disease may be reasonable in
very carefully selected patients. Furthermore, as systemic chemotherapy becomes more effective, the ability
to treat patients with oligometastatic disease, as well as select patients who may benefit from resection may
improve. As molecular data emerge, targeted approaches informed by the underlying genetic profile of a
specific pancreatic tumor may also help to tailor more personalized approaches to therapy.

Although the current standard of care for metastatic pancreatic adenocarcinoma is palliative chemotherapy
with no role for surgical resection, single institution experiences suggest that there may be a survival benefit
for resection of oligometastatic disease in select patients. Some centers have created algorithms to select
patients with more favorable tumor biology who might benefit from resection, applying such parameters as
response to chemotherapy and CA 19-9 values. It appears that morbidity and mortality is slightly higher for
hepatic compared with pulmonary metastatic resection. If surgery is being considered for oligometastatic
disease, surgical resection should be combined with systemic and patients need to very carefully selected.

There are no randomized controlled trials exist, and current data are based on small, retrospective
observational studies with varying definitions of oligometastasis and different inclusion criteria, extent of
metastasectomy, timing and regimens of systemic therapy, and reference groups for comparison. As such, the
level of evidence to suggest a benefit for resection of oligometastatic disease remains low.

Of note, there is an ongoing multicenter, randomized, controlled phase III trial called CSPAC-1
(NCT03398291) in China evaluating the possible benefit of simultaneous resection of pancreatic cancer
[39]
and liver oligometastases after induction chemotherapy . Inclusion criteria include age 18-75, Eastern
Cooperative Oncology Group performance status 0-1, and histologically-confirmed stage IV pancreatic
cancer with no more than 3 liver metastases. Patients who meet inclusion criteria for intervention, including
resectable primary tumor and liver lesions, no new metastatic disease, and a drop in abnormal tumor
markers by more than 50% after chemotherapy, are eligible for synchronous resection of the primary
pancreatic cancer and the liver metastasis. Patients will randomized to chemotherapy and resection
versus standard chemotherapy. The primary outcome measure is overall survival from start of induction
chemotherapy, and secondary outcomes include overall survival after completing induction chemotherapy,
quality of life, and post-operative morbidity and mortality. The expected completion date of the study is
2025. Until randomized data are available, resection of oligometastatic disease of the liver and lung in PDAC
should only be done in a multi-disciplinary setting for highly selected patients and, preferably, on a protocol
basis.