Locally advanced mid/low rectal cancer with synchronous resectable liver metastases: systematic review of the available strategies and outcome.

The management of patients with locally advanced mid/low rectal cancer with resectable liver metastases is complex because of the need to combine the optimal treatment of both tumors. This study aims to review the available treatment strategies and compare their outcome, focusing on radiotherapy (RT) and liver-first approach (LFA). A systematic review was performed in PubMed, Embase, and web sources including articles published between 2000 and 02/2023 and reporting mid-/long-term outcomes. Overall, twenty studies were included (n = 1837 patients). Three- and 5-year overall survival (OS) rates were 51-88% and 36-59%. Although several strategies were reported, most patients received RT (1448/1837, 79%; > 85% neoadjuvant). RT reduced the pelvic recurrence risk (5.8 vs. 13.5%, P = 0.005) but did not impact OS. Six studies analyzed LFA (n = 307 patients). LFA had a completion rate similar to the rectum-first approach (RFA, 81% vs. 79%) but the interval strategy-an LFA variant with liver surgery in the interval between radiotherapy and rectal surgery-had a better completion rate than standard LFA (liver surgery/radiotherapy/rectal surgery, 92% vs. 75%, P = 0.011) and RFA (79%, P = 0.048). Across all series, LFA achieved the best survival rates, and in one paper it led to a survival advantage in patients with multiple metastases. In conclusion, different strategies can be adopted, but RT should be included to decrease the pelvic recurrence risk. LFA should be considered, especially in patients with high hepatic tumor burden, and RT before liver surgery (interval strategy) could maximize its completion rate.