Locoregional Treatment of Metastatic Pancreatic Cancer Utilizing Resection, Ablation and Embolization: A Systematic Review

Abstract

The prognosis of metastatic pancreatic ductal adenocarcinoma (mPDAC) remains universally poor, requiring new and innovative treatment approaches. In a subset of oligometastatic PDAC patients, locoregional therapy, in addition to systemic chemotherapy, may improve survival. The aim of this systematic review was to explore and evaluate the current evidence on locoregional treatments for mPDAC. A systematic literature search was conducted on locoregional techniques, including resection, ablation and embolization, for mPDAC with a focus on hepatic and pulmonary metastases. A total of 59 studies were identified, including 63,453 patients. Although subject to significant bias, radical-intent local therapy for both the primary and metastatic sites was associated with a superior median overall survival from metastatic diagnosis or treatment (hepatic mPDAC 7.8-19 months; pulmonary mPDAC 22.8-47 months) compared to control groups receiving chemotherapy or best supportive care (hepatic mPDAC 4.3-7.6 months; pulmonary mPDAC 11.8 months). To recruit patients that may benefit from these local treatments, selection appears essential. Most significant is the upfront possibility of local radical pancreatic and metastatic treatment. In addition, a patient's response to neoadjuvant systemic chemotherapy, performance status, metastatic disease load and, to a lesser degree, histological differentiation grade and tumor marker CA19-9 serum levels, are powerful prognostic factors that help identify eligible subjects. Although the exact additive value of locoregional treatments for mPDAC patients cannot be distillated from the results, locoregional primary pancreatic and metastatic treatment seems beneficial for a highly selected group of oligometastatic PDAC patients. For definite recommendations, well-designed prospective randomized controlled trials with strict in- and exclusion criteria are needed to validate these results.

Keywords: ablation; embolization; locoregional treatment; metastatic pancreatic cancer; oligo-metastases; resection.

Figure 1

Flow diagram of the systematic search according to PRISMA [16].

Figure 2

Randomized controlled trial (RCT) design. Two potential setups of an RCT to determine the possible life-prolonging value of locoregional treatment in synchronous (left) or metachronous (right) metastatic PDAC (mPDAC). The RCTs adhere to four main selection pillars: patient fitness, prior systemic treatment, pancreatic tumor and metastatic disease. Selection criteria include WHO performance status 0–2, partial response (PR) or stable disease (SD) after neoadjuvant chemotherapy, having a resectable primary tumor (synchronous mPDAC), metastatic disease confined to the liver and ≤5 metastases that are locally treatable. For metachronous mPDAC, the pancreatic tumor has to be resected previously, without evidence of local recurrence. In addition to the main criteria, several supportive selection criteria are portrayed (dotted outline), which may or may not be used, including a decrease of ≥20–50% in tumor marker CA19-9 serum levels after chemotherapy, lower histological grade (well/moderately differentiated), non-squamous transcriptomic subtype and, in case of metachronous mPDAC, an R0 resection margin of the primary tumor. If mPDAC patients meet all these requirements, they can be randomized into either a radical locoregional treatment group or a control group receiving chemo(radio)therapy. * After primary resection but prior to metastatic treatment.