Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases?

BACKGROUND: Chemotherapy is increasingly used in colorectal liver metastases (CRLMs) even when they are initially resectable. The aim of our study was to address the still pending question of whether perioperative chemotherapy is really beneficial in patients developing solitary metastases at a distance from surgery of the primary.

METHODS: We analyzed a multicentric cohort of 1471 patients resected for solitary, metachronous, primarily resectable CRLMs without extrahepatic disease in the LiverMetSurvey International Registry over a 15-year period. Patients who received at least 3 cycles of oxaliplatin- or irinotecan-based chemotherapy before liver surgery (group CS, n = 169) were compared with those who were resected upfront (group S, n = 1302).

RESULTS: Patients of group CS were more frequently females (49% vs 36%, P = 0.001) and had larger metastases (≥5 cm, 33% vs 23%, P = 0.007); no difference was observed with regard to age, site of the primary tumour, time delay to occurrence of metastases, and carcinoembryonic antigen (CEA) levels at the time of diagnosis in the 2 groups. The rate of postoperative complications was significantly higher in group CS (37.2% vs 24% in group S, P = 0.006). At univariate analysis, preoperative chemotherapy did not impact the overall survival (OS) (60% at 5 years in both groups); however, postoperative chemotherapy was associated with better OS (65% vs 55% at 5 years, P < 0.01). At multivariate analysis, age 70 years or older (P = 0.05), lymph node positivity in the primary tumor (P = 0.02), a primary-to-metastases time delay of less than 12 months (P = 0.04), raised CEA levels of more than 5 ng/mL at diagnosis (P < 0.01), a tumor diameter of 5 cm or more (P < 0.01), noncurative liver resection (P < 0.01), and the absence of postoperative chemotherapy (P < 0.01) were independent prognostic factors of survival. The disease-free survival (DFS) was negatively influenced by CEA level of more than 5 ng/mL (P < 0.01), size of the metastases 5 cm or more (P = 0.05), and the absence of postoperative chemotherapy (P < 0.01). When patients with metastases of less than 5 cm in size were compared to those with metastases of size 5 cm or more, preoperative chemotherapy did not influence the OS or DFS in either group. Postoperative chemotherapy, on the other hand, improved OS and DFS in patients with metastases of size 5 cm or more but not in patients with metastases of less than 5 cm in size.

CONCLUSIONS: Although preoperative chemotherapy does not seem to benefit the outcome of patients with solitary, metachronous CRLM, postoperative chemotherapy is associated with better OS and DFS, mainly when the tumor diameter exceeds 5 cm.