Histological tumor response assessment in colorectal liver metastases after neoadjuvant chemotherapy: impact of the variation in tumor regression grading and peritumoral lymphocytic infiltration

Background: The objective of this study was to evaluate the prognostic value of the variation in tumor regression grade (TRG) and peritumoral lymphocytic infiltration of colorectal liver metastases (CRLMs) after neoadjuvant chemotherapy (NACT). Methods: A retrospective review was performed in 98 patients with CRLMs who underwent NACT between 2010 and 2016. The TRG scores and counts of TILs at the tumor-normal interface were assessed in all 176 resected liver metastases to determine their association with prognosis. According to the variation in TRG scores, 40 patients with more than one liver metastasis were divided into a decreased TRG group and a stable TRG group. An additional independent cohort of 64 patients with 106 resected liver specimens was established to validate our main findings. Results: In the derivation cohort of 98 patients, 41.8% patients had a favourable pathological response to NACT (TRG 1-3), which were significantly associated with improved prognosis. Seventeen patients (42.5%) showed decreased TRG scores, and the remaining patients had stable scores. The multivariate analysis indicated that patients with decreased TRG scores had a better recurrence-free survival (RFS) compared with those with stable TRG scores (HR=0.42, P=0.034), and a similar trend was observed in the validation cohort (P=0.068). Dense TILs surrounding the metastases were present in 55.1% of the derivation cohort and associated with pathological response (P=0.008). Among patients with a pathological response to NACT, those with dense TILs had a superior RFS compared to those with weak TILs in both cohorts (derivation: HR=0.36, P=0.035; validation: HR=0.34, P=0.016). Conclusions: Variation in TRG scores and peritumoral lymphocytic infiltration may be proposed as secondary pathological parameters to evaluate the pathological response to NACT and predict the risk of recurrence after liver surgery.