Surgical resection of pancreatic cancer with synchronous hepatic oligometastases: Real benefit or selection bias?

Background

Most patients with pancreatic cancer have synchronous metastatic disease. Hepatic metastases have traditionally been considered a contraindication for surgery. However, the success of hepatic metastasectomy in other malignancies has raised interest for this procedure also in pancreatic cancer. ¹

Oligometastases is defined as a limited metastatic burden. There is still no consensus on the definition, and some define hepatic oligometastases in terms of number, usually less than five metastatic lesions.^2,3

Those in favor of performing synchronous hepatic resections in oligometastatic disease highlight the safety of pancreatic and liver surgery (high-volume centers) and the importance of achieving a macroscopically radical operation. The aggressive tumor biology of pancreatic cancer, though, imply that it is a systemic disease that cannot be cured with local measures.

Small single- and multicenter series have evaluated the outcomes of resection of both the primary tumor and synchronous hepatic oligometastases in pancreatic cancer,^1,2,4,5 either upfront resections or conversion surgery after neoadjuvant treatment. Most hepatic resections were minor. The median overall survival was 7.6–14.5 months after upfront resection and 34–56 months after neoadjuvant treatment.^1,2,4,5

Previous studies seem encouraging, but have limitations, mostly being small retrospective series, with heterogenous patient cohorts, unclear motivation for the decision to resect or not, and lack of control groups.

Prospective clinical trials are needed. The Chinese Study Group for Pancreatic Cancer (CSPAC)-1 trial (NCT03398291) is a multicenter, prospective, randomized phase III control trial, evaluating a strategy for selecting pancreatic cancer patients with hepatic oligometastases who may benefit from synchronous resection after conversion chemotherapy. ³ The Hepatic Oligometastatic Pancreatic Cancer (HOLIPANC) study (NCT04617457) is a non-randomized, multicenter, single-arm phase II clinical trial for pancreatic cancer patients with hepatic oligometastases receiving neoadjuvant combination chemotherapy, where those with stable or responsive disease and a resectable primary tumor will undergo synchronous resection of the tumor and hepatic metastases. ⁶ The SCANPAN-1 trial (NCT05271110) is a Scandinavian multicenter study that will prospectively investigate the role of surgery or ablation of liver metastases from pancreatic cancer.

In summary, there is no high-level evidence showing benefit of resection of synchronous hepatic oligometastases. Furthermore, it is unknown what kind of liver resection for oligometastases with pancreatic resection is safe (minor or major resection). Randomized trials are currently lacking, and until then hepatic metastasectomy in pancreatic cancer should only be performed in a research setting. Molecular subtyping and information on tumor biology, including tumor aggressiveness and chemosensitivity, may aid in treatment planning and patient selection.