Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

Florian E Buisman,Pieter M H Nierop,Eran Sadot,Peter B Vermeulen,Michael D’Angelica,Vinod P Balachandran,William R Jarnagin,Bas Groot Koerkamp,Eric P Van Der Stok,T Peter Kingham,Jinru Shia,Dirk J Grünhagen,Diederik J Höppener,Robert R J Coebergh Van Den Braak,Cornelis Verhoef,Boris Galjart,John M Creasy

doi:10.1007/s10585-020-10048-w

Abstract

Adjuvant systemic chemotherapy (CTx) is widely administered in patients with colorectal liver metastases (CRLM). Histopathological growth patterns (HGPs) are an independent prognostic factor for survival after complete resection. This study evaluates whether HGPs can predict the effectiveness of adjuvant CTx in patients with resected CRLM. Two main types of HGPs can be distinguished; the desmoplastic type and the non-desmoplastic type. Uni- and multivariable analyses for overall survival (OS) and disease-free survival (DFS) were performed, in both patients treated with and without preoperative chemotherapy. A total of 1236 patients from two tertiary centers (Memorial Sloan Kettering Cancer Center, New York, USA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands) were included (period 2000–2016). A total of 656 patients (53.1%) patients received preoperative chemotherapy. Adjuvant CTx was only associated with a superior OS in non-desmoplastic patients that had not been pretreated (adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.37–0.73, p < 0.001), and not in desmoplastic patients (adjusted HR 1.78, 95% CI 0.75–4.21, p = 0.19). In pretreated patients no significant effect of adjuvant CTx was observed, neither in the desmoplastic group (adjusted HR 0.83, 95% CI 0.49–1.42, p = 0.50) nor in the non-desmoplastic group (adjusted HR 0.96, 95% CI 0.71–1.29, p = 0.79). Similar results were found for DFS, with a superior DFS in non-desmoplastic patients treated with adjuvant CTx (HR 0.71, 95% CI 0.55–0.93, p < 0.001) that were not pretreated. Adjuvant CTx seems to improve OS and DFS after resection of non-desmoplastic CRLM. However, this effect was only observed in patients that were not treated with chemotherapy.

Highlights

Pre- and or postoperative systemic chemotherapy is often administered in patients with potentially resectable colorectal liver metastases (CRLM)
This study investigates whether histopathological growth patterns predict the effect of adjuvant systemic chemotherapy after resection of CRLM
The results suggest that Histopathological growth patterns (HGPs), that are assessed after resection of CRLM, are associated with the effectiveness of adjuvant CTx

Summary

Introduction

Pre- and or postoperative systemic chemotherapy is often administered in patients with potentially resectable colorectal liver metastases (CRLM). The effectiveness has been investigated in randomized controlled trials [1,2,3,4]. The longterm follow-up of a phase III trial demonstrated a superior early progression-free survival (PFS) for patients treated with perioperative FOLFOX. There was no difference in overall survival (OS) with long term follow-up [5]. Retrospective studies have suggested that the effectiveness of systemic chemotherapy may depend on the extent of disease or factors associated with OS. Positive associations of perioperative systemic chemotherapy and OS were seen in populations with a high clinical risk score (CRS), or elevated preoperative carcinoembryonic

Methods

Results

Conclusion