Complete pathological response of colorectal liver metastases after neoadjuvant chemotherapy: myth or reality?

4063 Background: A complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy has been shown unrelated to the real disappearance of active tumor. By contrast, a complete pathological response (PCR) could be more clinically relevant, but has not been explored. The aim of this study was to evaluate the incidence and outcome as well as predictive factors of PCR, in patients resected from CLM after neoadjuvant chemotherapy. Methods: In our institution 791 consecutive patients with CLM underwent liver resection after neoadjuvant chemotherapy. CCR was defined as the disappearance of all lesions after chemotherapy, and PCR was defined as the total necrosis of all metastases on the resection specimen. Both were selected from a prospective database. Patients with and without PCR were compared, survivals were determined and predictive factors for PCR were analyzed using a multivariate risk model. Results: There were 0.4% CCR (3/791) and 4% PCR (31/791). Among the 31 patients with PCR, the median number of CLM was 2.0 (range 1–13) with a maximum diameter = 3 cm for most cases (73%) at diagnosis. Ten patients (32%) had extrahepatic metastases. Compared to patients without PCR, patients with PCR were younger (p< 0.05) and had a smaller maximum tumor size (p=0.007). Rate of objective response was higher (81% vs. 52%; p=0.002) and last chemotherapy regimen contained more frequently oxaliplatin than irinotecan (p=0.05). Number of chemotherapy cycles and treatment lines were not different. At multivariate analysis, 4 predictive factors of PCR were identified: age = 60 yrs, maximum size at diagnosis = 3 cm, CEA = 40 ng/ml at diagnosis and achievement of an objective response. The probability of PCR ranged from 0.2% when all were absent to 33.8% when all were present. PCR strongly impacted overall survival (OS) that was 69% and 62% at 5 and 10 years with a disease-free survival (DFS) of 42% for both. Conclusions: PCR concerns overall 4% of patients receiving neoadjuvant chemotherapy allowing for surgery, but as much as one third of those aged less than 60 years, developing response on liver metastases smaller than 3 cm, with low CEA values. Uncommon high survival rates are observed in this setting. PCR more than CCR is a reality and strongly impacts patient outcome. No significant financial relationships to disclose.