Staged or Simultaneous Surgery for Colon or Rectal Cancer with Synchronous Liver Metastases: Implications for Study Design and Clinical Endpoints

SIMPLE SUMMARY: Patients who present with a primary colon or rectal cancer and are diagnosed with liver metastases at the same time (synchronous liver metastasis) have a number of treatment options when considering management. Providing systemic disease control alone involves several treatment considerations. For surgery, the decision rests with treating the primary tumor first, the liver metastasis first, or resection of both disease locations in one procedure. The decision rests on several conditions. Designing a trial to take all these factors into account while maintaining a reasonable endpoint for patients and caregivers is not straightforward. Here, we discuss some of the underlying points when considering simultaneous resection of colon or rectal cancer with liver metastases. ABSTRACT: In patients presenting with colorectal cancer and synchronous liver metastases, the disease burden related to the liver metastasis is the driving cause of limited longevity and, eventually, risk of death. Surgical resection is the potentially curative treatment for colorectal cancer liver metastases. In the synchronous setting where both the liver metastases and the primary tumor are resectable with a relative low risk, the oncological surgeon and the patient may consider three potential treatment strategies. Firstly, a “staged” or a “simultaneous” surgical approach. Secondly, for a staged strategy, a ‘conventional approach’ will suggest removal of the primary tumor first (either colon or rectal cancer) and plan for liver surgery after recovery from the first operation. A “Liver first” strategy is prioritizing the liver resection before resection of the primary tumor. Planning a surgical trial investigating a two-organ oncological resection with highly variable extent and complexity of resection as well as the potential impact of perioperative chemo(radio)therapy makes it difficult to find the optimal primary endpoint. Here, we suggest running investigational trials with carefully chosen composite endpoints as well as embedded risk-stratification strategies to identify subgroups of patients who may benefit from simultaneous surgery.