Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy

Abstract

Peritoneal Carcinomatosis (PC) is a late stage manifestation of several gastrointestinal malignancies including appendiceal, colorectal, and gastric cancer. In PC, tumors metastasize to and deposit on the peritoneal surface and often leave patients with only palliative treatment options. For colorectal PC, median survival is approximately five months, and palliative systemic therapy is able to extend this to approximately 12 months. However, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent is possible in some patients with limited tumor burden. In well-selected patients undergoing complete cytoreduction, median survival has been reported as high as 63 month. Identifying patients earlier who are either at risk for, or who have recently developed PC may provide them with additional treatment options such as CRS/HIPEC. PC is diagnosed late by imaging findings or often times during an invasive procedures such as laparoscopy or laparotomy. In order to improve the outcomes of PC patients, a minimally invasive, accurate, and specific PC screening method needs to be developed. By utilizing circulating PC biomarkers in the serum of patients, a "liquid biopsy," may be able to be generated to allow a tailored treatment plan and early intervention. Exosomes, stable patient-derived nanovesicles present in blood, urine, and many other bodily fluids, show promise as a tool for the evaluation of labile biomarkers. If liquid biopsies can be perfected in PC, manifestations of this cancer may be more effectively treated, thus offering improved survival.

Keywords: biomarker; exosomes; liquid biopsy; peritoneal carcinomatosis.

Figure 1. Peritoneal Cancer Index (PCI) scoring system

PCI is a diagnostic and prognostic tool that is a sum of scores in thirteen abdominal regions. Each receives a score of 0-3 based on the largest tumor size in each region. Scores range from 0 to 39. Higher scores indicate more widespread and/or larger tumors in the peritoneal cavity.

Figure 2. Tumor Cells release nanovesicles called exosomes which carry RNAs, including microRNAs and messenger RNAs, and proteins