Pancreatic cancer is a highly aggressive disease, with advanced-stage diagnosis being the
most common presentation, where surgery is usually contraindicated regardless of the
number and location of metastases. Among the various metastatic sites, liver involvement
is particularly common. The conventional approach for metastatic disease is systemic
chemotherapy, aimed at controlling tumor growth, reducing symptoms, and improving quality
of life. However, the role of aggressive local therapies, such as surgical removal of the
primary tumor and liver metastases, is under active investigation and clinical debate for
patients who show response or disease stability following chemotherapy treatment in the
context of oligometastatic disease. The oligometastatic stage, defined as the presence of
a limited number of metastatic lesions in specific organs, offers a potential opportunity
for locoregional interventions. Proponents of surgical intervention argue that complete
removal of the tumor following optimal first-line systemic therapy may eradicate the
primary cancer source and eliminate or control metastatic sites. This approach could
potentially improve disease control, survival, and quality of life for selected patients.
This prospective study thus aims to compare the efficacy and safety of a surgical
approach versus palliative treatment alone in patients with resectable oligometastatic
pancreatic cancer to the liver, with stable disease or therapeutic response following
first-line chemotherapy.
This is an international multicenter randomized controlled trial promoted by the
University of Padua. The study aims to enroll 28 patients per arm, for a total of 56. The
study will include adult patients aged 18 years or older with cytologically or
histologically confirmed pancreatic adenocarcinoma and radiologically documented liver
metastases. Eligible patients must present with synchronous oligometastatic disease,
defined as a limited number of liver metastases (up to 3 lesions) without evidence of
extrahepatic metastases, based on a multidisciplinary discussion. The primary pancreatic
tumor must still be present at the time of enrollment. Enrolled patients must have
received at least 6 months of systemic chemotherapy. Eligible patients with
response/stability after first-line chemotherapy will undergo either surgical resection
or continuous chemotherapy, depending on the arm to which they are randomized. Patients
will be assigned in a 1:1 ratio to either the surgical resection arm (n=28) or the
palliative care arm (n=28). Randomization will be performed centrally using a
computer-generated randomization sequence. Stratification factors, such as ECOG
Performance Status, serum Ca 19-9 level at enrollment, primary pancreatic tumor location,
and participating center, will be used to ensure balance between the two study arms. Due
to the nature of the interventions, it is not feasible to blind patients and treating
physicians to treatment allocation. Upon enrollment, the patient must consent to
participate in the above-described randomized study. The two randomization arms are as
follows:
A) Surgical Resection Arm: Patients in this arm will undergo surgical resection of both
the primary tumor and liver metastases. The surgical approach, extent of resection, and
perioperative management will follow the standard protocols of each participating center.
Venous vascular resections may be performed to achieve oncologic radicality. Standard or
parenchyma-sparing liver resections may be conducted for the resection of liver
metastases. Alternatively, percutaneous or microwave ablation of liver lesions <20 mm is
possible if technically feasible. Postoperative chemotherapy and/or radiotherapy may be
administered based on multidisciplinary decisions and individual case evaluations.
B) Palliative Care Arm: Patients in this arm will continue to receive palliative care,
consisting of observation or continuation of chemotherapy based on the investigator's
choice and the duration of first-line chemotherapy. If necessary, they will continue with
systemic chemotherapy, as received during the initial treatment phase, following an
institution-approved chemotherapy protocol adapted to the attending physician's
preference. Patients will undergo regular evaluations at predefined intervals throughout
the study period. These evaluations will include clinical assessments, laboratory tests,
radiologic imaging (such as abdominal and chest CT scans with contrast), quality-of-life
assessments, and nutritional evaluations. The frequency of evaluations may vary depending
on the study phase but will generally occur every 8-12 weeks according to clinical
practice. These assessments will provide data on primary and secondary endpoints. The
minimum follow-up specified by the study protocol is 2 years from randomization.
