Retrospective Analysis of Patients with Signet Ring Subtype of Colorectal Cancer with Peritoneal Metastasis Treated with CRS & HIPEC.

Aruna Prabhu,Akiyoshi Mizumoto,Shouzou Sako,Yutaka Yonemura,Kousuke Noguchi,Yang Liu,Shunsuke Motoi,Satoshi Wakama,Andreas Brandl,Haruaki Ishibashi,Masumi Ichinose,Nobuyuki Takao

doi:10.3390/cancers12092536

Abstract

Simple SummaryApproximately 1% of all patients with colorectal cancer, and 15% of patients with peritoneal metastasized colorectal cancer present with the subtype of signet ring cell, which is associated with inferior oncological outcome and reduced overall survival. The evidence whether patients with signet ring cell subtype are benefiting from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is limited. The aim of this large bicentric retrospective study including 60 patients with this subtype was to explore the survival and define predictive factors of these patients. Median overall survival was 14.4 months, while small bowel PCI > 2 (HR: 6.5; p = 0.008) was the strongest predictive factor for inferior patient survival. The study concludes, that after thoroughly selection patients for CRS and HIPEC, even patients with signet ring cell subtype of colorectal cancer may benefit from this concept. Signet ring cell subtype (SRC) of colorectal cancer (CRC) is a rare subtype and occurs in approximately 1% of all patients with CRC. Patients with peritoneal metastasis (PM) of SRC have a poor prognosis, and this subtype is frequently considered as a contra-indication for extensive surgical treatment. This retrospective study from two dedicated peritoneal surface malignancy centers in Japan included all patients treated with CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between July 1994 and December 2017 from a prospectively maintained database. Preoperative, operative, and postoperative parameters were recorded, including complication rates and follow-up. Sixty of the 320 patients treated with CRS due to CRC were diagnosed with SRC subtype. The mean age of the patients was 51.4 years, and the mean peritoneal carcinomatosis index (PCI) was 13.1. Complete cytoreduction was achieved in 61.7% of cases. The postoperative morbidity rate was 25% and the mortality rate was 1.7%. The median overall survival (OS) was 14.4 months. Cox regression analysis revealed small bowel PCI > 2 (hazard ratio (HR) 6.5; p = 0.008) as the most important factor for OS. With accurate patient selection (e.g., PCI ≤ 12 or small bowel PCI ≤ 2), even patients with PM of CRC with SRC subtype may benefit from CRS and HIPEC, with median OS from 17.8 to 20.8 months and 5-year OS of 11.6%.

Highlights

Peritoneal metastases (PMs) in colorectal cancer (CRC) are diagnosed in 4–10% of patients at the initial diagnosis
The reported median overall survival (OS) for patients treated with systemic chemotherapy with or without targeted therapy is in the range of 10–12 months for patients with PM
With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), there has been a significant improvement in median OS in selected patients

Summary

Introduction

Peritoneal metastases (PMs) in colorectal cancer (CRC) are diagnosed in 4–10% of patients at the initial diagnosis. 15–20% of patients develop peritoneal recurrent disease [1,2,3,4]. These patients are commonly treated with palliative chemotherapy with or without palliative surgery. The reported median overall survival (OS) for patients treated with systemic chemotherapy with or without targeted therapy is in the range of 10–12 months for patients with PM compared to 17–22 months for patients without PM [5,6,7,8]. With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), there has been a significant improvement in median OS in selected patients. Elias et al reported a median survival of 63 months in these patients when treated with CRS and HIPEC [9]

Methods

Discussion

Conclusion