Treatment-sequencing before and after index hepatectomy with either synchronous or metachronous colorectal liver metastasis: Comparison of recurrence risk, repeat hepatectomy and overall survival in a population-derived cohort.

Background: Treatment of colorectal cancer liver metastasis (CRLM) includes several options with impact on the patient journey and may depend on presentation and patient characteristics. The aim of the study was to investigate how treatment sequencing in index hepatectomy for synchronous or metachronous CRLM may potentially impact treatment pathways and oncological outcomes.

Methods: An observational cohort study (ACROBATICC; NCT0176813) of patients having surgery for CRLM. Patient and tumour characteristics, treatment and recurrence patterns were recorded. Recurrence-free (RFS) and overall survival (OS) analyzed by Kaplan-Meier method (log-rank test).

Results: The study included 132 patients, median age 67 yrs, 69 % men and 55 % had synchronous CRLM. Overall, 65 (50 %) received neoadjuvant chemotherapy, 45 (63 %) in synchronous and 20 (33 %) in metachronous CRLM (odds ratio, OR 0.30 95%CI 0.15-0.62; p < 0.001). Patient- and tumour characteristics did not differ except number of metastases (synchronous CRLM median 2 (range 1-4) vrs metachronous median 1 (1-2), respectively; p < 0.001). Some 99 (75 %) patients relapsed, 38 % had liver-recurrence. Repeat hepatectomy was performed in one-third, with equal rates between synchronous or metachronous CRLM. Median OS of all patients was 68 months, for a difference of 24 months between synchronous and metachronous CRLM (59 and 83 months, respectively; p = 0.334). RFS survival did not differ between groups.

Conclusion: Pre-operative chemotherapy was given twice as often for patients with synchronous CRLM who also had more metastases and more frequently rectal primaries. Liver recurrence rates, repeat hepatecomy and overall survival was comparable between groups. Intrinsic cancer biology needs to be better investigated to provide better outcomes.