Published online Apr 15, 2019. doi: 10.4251/wjgo.v11.i4.295
Peer-review started: October 2, 2018
First decision: October 25, 2018
Revised: November 27, 2018
Accepted: December 31, 2018
Article in press: January 1, 2019
Published online: April 15, 2019
Colorectal cancer is the third most common cancer in men and the second most common in women worldwide. Almost a third of the patients has or will develop liver metastases. Neoadjuvant chemotherapy (NAC) has recently become nearly systematic prior to surgery of colorectal livers metastases (CRLMs). The response to NAC is evaluated by radiological imaging according to morphological criteria. More recently, the response to NAC has been evaluated based on histological criteria of the resected specimen. The most often used score is the tumor regression grade (TRG), which considers the necrosis, fibrosis, and number of viable tumor cells.
To analyze the predictive factors of the histological response, according to the TRG, on CRLM surgery performed after NAC.
From January 2006 to December 2013, 150 patients who had underwent surgery for CRLMs after NAC were included. The patients were separated into two groups based on their histological response, according to Rubbia-Brandt TRG. Based on their TRG, each patient was either assigned to the responder (R) group (TRG 1, 2, and 3) or to the non-responder (NR) group (TRG 4 and 5). All of the histology slides were re-evaluated in a blind manner by the same specialized pathologist. Univariate and multivariate analyses were performed.
Seventy-four patients were classified as responders and 76 as non-responders. The postoperative mortality rate was 0.7%, with a complication rate of 38%. Multivariate analysis identified five predictive factors of histological response. Three were predictive of non-response: More than seven NAC sessions, the absence of a radiological response after NAC, and a repeat hepatectomy (P < 0.005). Two were predictive of a good response: A rectal origin of the primary tumor and a liver-first strategy (P < 0.005). The overall survival was 57% at 3 yr and 36% at 5 yr. The disease-free survival rates were 14% at 3 yr and 11% at 5 yr. The factors contributing to a poor prognosis for disease-free survival were: No histological response after NAC, largest metastasis > 3 cm, more than three preoperative metastases, R1 resection, and the use of a targeted therapy with NAC (P < 0.005).
A non-radiological response and a number of NAC sessions > 7 are the two most pertinent predictive factors of non-histological response (TRG 4 or 5).
Core tip: In this study, we analyzed the histological responses of colorectal liver metastasis from 74 responders and 76 non-responders after neoadjuvant chemotherapy. We identified that the absence of a radiological response and extended neoadjuvant chemotherapy, comprising more than seven treatment sessions, are the two most pertinent predictive factors of non-histological response. This study also confirmed that the histological response of colorectal liver metastases after neoadjuvant chemotherapy has an influence on survival and, hence, warrants consideration. However, this influence on overall survival was lacking in cases of particularly aggressive disease that revealed microscopic vascular invasion in histological analyses.