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.
Few studies to date have documented the influence of TRG on patient survival, and they were mostly published by the authors of the scoring systems. This explains why the histological regression score of CRLM specimens is rarely used in current practice[15,32]. Therefore, at present, analysis of the histological response by the TRG has no influence on whether or not adjuvant chemotherapy is administered. To our knowledge, no study has attempted to identify the predictive factors of histological response after NAC.
Our research aimed to analyze the histological response, according to the Rubbia-Brandt TRG, on CRLM surgery performed after NAC. It also sought to identify independent predictive factors of a good response, and to analyze the influence of this response on overall and disease-free survival.
From January 2006 to December 2013, 150 patients who had undergone 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 (NR): More than seven NAC sessions, absence of a radiological response after NAC, and repeat hepatectomy (P < 0.005). Two were predictive of a good response (R): 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. Factors contributing to a poor prognosis for the DFS 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).
The histological response of CRLMs after NAC has an influence on survival, hence warranting consideration. We found, however, that this influence on overall survival was lacking in cases of particularly aggressive disease, with microscopic vascular invasion upon histological analysis.
Two simple criteria enable the prediction of a histological response after NAC: More than seven treatment sessions and absence of a radiological response.