Optimal timing of systemic therapy in resectable colorectal liver metastases.

Colorectal cancer is a commonly encountered malignancy in surgical oncology. Stage distribution at diagnosis for colorectal cancer as reported in the Surveillance, Epidemiology and End Results database is put at 39.7, 35.9, 18.5, and 5.9 per cent, respectively, for localized, regional, distant, and unstaged tumors, respectively.1 The liver is a common site of disseminated disease with synchronous colorectal liver metastases (CLM) accounting for approximately 23 to 51 per cent of all patients undergoing surgical resection for liver metastases.2 Surgical resection of isolated CLM still offers the most durable chance for long-term survival despite remarkable advances in systemic chemotherapy. Historical data put five-year survival after resection at 35 per cent and relapse rate associated with resection at approximately 75 per cent.3 Recent data on survival outcome after resection of colorectal liver metastases put the five-year survival at 45 to 60 per cent up from 30 to 40 per cent.4–9 This witnessed improvement over the past two decades in the survival of patients diagnosed with colorectal liver metastases is attributed in part to better patient selection for surgical resection of hepatic metastases, improved surgical technique, perioperative care, and improvements in systemic chemotherapy.10–13 Modern systemic chemotherapeutic agents can increase the resection rates and improve relapse-free rates when used as adjuncts to surgical resection for CLM.14, 15 Preoperative or perioperative chemotherapy has been shown to improve the outcome of hepatic resections. Nordlinger et al.16 in the EORTC 40983 trial showed that perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and improved progression-free survival in eligible and resected patients. The use and safety of preoperative chemotherapy in patients diagnosed with resectable liver metastases was also demonstrated.16, 17 As a result of the documented activity of systemic chemotherapy in the perioperative setting for CLM, patients have been managed with different combinations of surgical resection and adjunctive systemic therapy. However, the most appropriate and effective timing of institution of systemic chemotherapy in the management algorithm for resectable CLM has not been well defined. We conducted a single-institutional review of patients who underwent surgical resection of CLM. The primary goal of our study was to assess whether the timing of institution of systemic therapy relative to surgical resection significantly impacted overall survival in this cohort of patients and secondarily to identify clinicopathologic factors that may have influenced when systemic therapy was administered.