Colorectal Cancer With Liver-limited Synchronous Metastases: an Inception Cohort Study of Standardised Care Pathways

Patients who present with metastatic liver disease following treatment of the primary (termed metachronous disease) receive care focused on this new metastatic disease. In contrast, the management of patients who present with colorectal cancer and concurrent liver metastases (synchronous metastasis) is more complex. These patients may have less favourable cancer biology and thus may be less likely to become long-term survivors. Logically, the management of patients with colorectal cancer with synchronous metastases can be dichotomised into those with hepatic disease together with extra-hepatic metastatic disease and those with liver-limited metastatic disease. In the first category, systemic chemotherapy is the mainstay of treatment advocated in current guidelines for patients with advanced multi-site metastatic (liver and systemic metastatic) disease of colorectal cancer origin.

The second category of patients with liver-limited synchronous metastases represents a complex and common clinical management problem. Traditional management (referred to variously as the classical or staged approach) comprised resection of the colorectal primary tumour followed by adjuvant chemotherapy with liver resection being undertaken as a subsequent operation. Advances in surgery, anaesthesia and critical care have made two alternative options feasible for patients with synchronous disease. The first is synchronous resection of the liver metastases and the colorectal primary. This has the attraction of removing the macroscopic tumour burden with a single operation. However, the morbidity of complex liver resection combined with major bowel resection may be considerable and there is some evidence of a negative effect on progression-free survival. The second option in the management of synchronous disease is resection of the liver metastatic disease as the first step, termed the reverse or liver-first approach. Liver-first surgery to manage synchronous colorectal cancer and liver metastatic disease has become more widely utilised because of oncological and technical developments. Oncologically, evidence of improved outcome in locally advanced rectal cancer treated by pre-operative chemo-radiotherapy prior to surgical resection creates a potential "window" in which liver resection may be undertaken. The technical development of colonic stenting permits symptoms associated with rectal cancer such as partial obstruction to be palliated without recourse to urgent bowel surgery. The liver-first strategy may be oncologically advantageous if liver metastatic disease rather than the primary cancer gives rise to systemic metastasis - although this is not established. A further potentially important benefit of the liver-first approach is that pelvic surgery may be either avoided or less extensive in patients with rectal tumours with a complete endoscopic, radiological and clinical response to chemo-radiotherapy.

Currently, evidence is inadequate to inform the selection of treatment for patients with colorectal cancer with synchronous liver-limited hepatic metastases. Specifically, in these patients, optimal pathways are not defined and there is a dearth of prospectively recorded cohort- defining factors influencing treatment selection or outcome. Given the treatment permutations to be understood, an inception cohort study would allow us to understand patient outcomes as a function of clinical decisions and patient/disease characteristics. By limiting care available to patients to a common evidence-informed pathway, sources of treatment variation can be minimised and, within a prospective design, data quality be optimised with respect to patient and treatment characteristics.

Following informed consent and recruitment, data will be collected on patients with colorectal cancer with liver-limited hepatic metastases including patient variables, treatment selection, factors influencing treatment, treatment-related morbidity and outcome. Regression modelling of findings will permit influences of patient and treatment factors upon outcomes to be quantified. Patterns of clinical decision making will help to understand the characteristics of patients for whom equipoise exists or is absent.