Impact of histological subtype on prognosis in stage IV colorectal cancer: A population-based cohort study.

Teppei Miyakawa,Shunji Kinuta,Satoru Shiraso,Hidetaka Kawamura,Shigeru Yamazaki,Yoshinao Takano,Shinichi Konno,Koji Kono,Atsushi Muto,Takahiro Kamiga,Toshiyasu Iwao,Naoyuki Yamashita,Michitaka Honda,Wen-Chi Chou

doi:10.1371/journal.pone.0264652

Abstract

BackgroundThere are a few established prognostic factors for stage IV colorectal cancer. Thus, this study aimed to evaluate the impact of histological subtypes on prognosis and metastatic patterns in patients with stage IV colorectal cancer.MethodsThis was a population-based, multicenter, cohort study. We included consecutive patients diagnosed with stage IV colorectal cancer between 2008 and 2015 at all designated cancer hospitals in Fukushima prefecture, Japan. Patients were classified into two groups according to histological subtypes as follows: poorly differentiated adenocarcinoma (Por), mucinous adenocarcinoma (Muc), or signet-ring cell carcinoma (Sig) and well (Wel) or moderately differentiated adenocarcinoma (Mod). We evaluated the relationship between these histological groups and survival time. After adjusting for other clinical factors, we calculated the hazard ratio for Por/Muc/Sig.ResultsA total of 1,151 patients were enrolled, and 1,031 and 120 had Wel/Mod and Por/Muc/Sig, respectively. The median overall survival was 19.2 and 11.9 months for Wel/Mod and Por/Muc/Sig, respectively (p < 0.001). The adjusted hazard ratio for Por/Muc/Sig with regard to survival time was 1.42 (95% confidence interval: 1.13–1.77). Por/Muc/Sig had a lower incidence of liver and lung metastases and a higher incidence of peritoneal dissemination and metastasis to rare organs, such as the bone and brain.ConclusionsThe Por/Muc/Sig histological subtype was an independent prognostic factor for poor prognosis among patients with stage IV colorectal cancer. The histological subtype may be useful for predicting the prognosis of patients with stage IV colorectal cancer and designing the treatment strategy.

Highlights

Recent advances in systemic chemotherapy, including targeted molecular agents, have contributed to the improvement of survival rates, the prognosis of stage IV colorectal cancer (CRC) with distant metastasis remains poor [1]
Patients were classified into two groups according to histological subtypes as follows: poorly differentiated adenocarcinoma (Por), mucinous adenocarcinoma (Muc), or signet-ring cell carcinoma (Sig) and well (Wel) or moderately differentiated adenocarcinoma (Mod)
The histological subtype may be useful for predicting the prognosis of patients with stage IV colorectal cancer and designing the treatment strategy

Summary

Introduction

Recent advances in systemic chemotherapy, including targeted molecular agents, have contributed to the improvement of survival rates, the prognosis of stage IV colorectal cancer (CRC) with distant metastasis remains poor [1]. Both primary and metastatic sites need to be considered in the treatment strategy, and in many cases, multiple surgeries or long-term chemotherapy are required. Por/Muc/Sig CRC is genetically known to have a high incidence of deficient mismatch repair (dMMR), which causes microsatellite instability (MSI) and BRAF mutations [2, 4–7] These genetic statuses are associated with a poor prognosis in stage IV CRC [8]. This study aimed to evaluate the impact of histological subtypes on prognosis and metastatic patterns in patients with stage IV colorectal cancer

Objectives

Methods

Conclusion