Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries and pathological tumor response on long-term survival

AbstractObjective: We analyzed the impact of chemotherapy-related liver injuries (CALI) and pathological tumor regression grade (TRG) on long-term prognosis in patients undergoing liver resection for colorectal metastases (CRLM). Background: CALI worsen the short-term outcomes of liver resection, but their impact on prognosis is unknown. Recently, a prognostic role of TRG has been suggested.Methods: Patients undergoing liver resection for CRLM between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based pre-operative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI and TRG.Results: 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), nodular regenerative hyperplasia in 63 (19.5%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG1-2 (major response), 21.4% had TRG3 (partial response), and 55.7% had TRG4-5 (no response). The higher the SOS grade the lower the pathological response: TRG1-2 and TRG4-5 occurred in 16.9% and 64.5% of patients with grade 2-3 SOS vs. 26.6% and 50.3% of patients with grade 0-1 SOS, respectively (p=0.036). After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival 52.5% vs. 35.2%, p=0.003). TRG stratified patient prognosis: 5-year survival 60.4% in TRG1-2, 40.2% in TRG3, and 29.8% in TRG4-5 (p=0.007). Microvascular and biliary invasion were present in 37.8% and 5.6% of patients and negatively impacted outcome (5-year survival 23.3% vs. 45.7% if absent [p=0.024] and 0% vs. 42.1% [p=0.026], respectively). Conclusions: CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. TRG was confirmed to be a crucial prognostic determinant, overcoming traditional morphological parameters. Steatosis was found to have a protective effect on survival. Identification of microvascular and biliary invasion contributed to prognosis assessment.