Colorectal Peritoneal Metastases: A Systematic Review of Current and Emerging Trends in Clinical and Translational Research

Abstract

Colorectal peritoneal metastases (CPM) are associated with abbreviated survival and significantly impaired quality of life. In patients with CPM, radical multimodality treatment consisting of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has demonstrated oncological superiority over systemic chemotherapy alone. In highly selected patients undergoing CRS + HIPEC, overall survival of over 60% has been reported in some series. These are patients in whom the disease burden is limited and where the diagnosis is made at an early stage in the disease course. Early diagnosis and a deeper understanding of the biological mechanisms that regulate CPM are critical to refining patient selection for radical treatment, personalising therapeutic approaches, enhancing prognostication, and ultimately improving long-term survivorship. In the present study, we outline three broad themes which represent critical future research targets in CPM: (1) enhanced radiological strategies for early detection and staging; (2) identification and validation of translational biomarkers for diagnostic, prognostic, and therapeutic deployment; and (3) development of optimized approaches for surgical cytoreduction as well as more precise strategies for intraperitoneal drug selection and delivery. Herein, we provide a contemporary narrative review of the state of the art in these three areas. A systematic review in accordance with PRISMA guidelines was undertaken on all English language studies published between 2007 and 2017. In vitro and animal model studies were deemed eligible for inclusion in the sections pertaining to biomarkers and therapeutic optimisation, as these areas of research currently remain in the early stages of development. Acquired data were then divided into hierarchical thematic categories (imaging modalities, translational biomarkers (diagnostic/prognostic/therapeutic), and delivery techniques) and subcategories. An interactive sunburst figure is provided for intuitive interrogation of the CPM research landscape.

Spectral photon-counting CT imaging of colorectal peritoneal metastases: initial experience in rats

“…It is of note that the diagnostic performance SPCCT was found to be in line with that reported for colorectal PM in humans using conventional CT, i.e. Se ranging, in function of lesion size and location, from 11 to 96% and Sp ranging from 49 to 100% 49 . However, in terms of absolute size, the Se of SPCCT in rats was much greater for lesions < 5 mm (LS-1 + LS-2) than the 11% Se for such lesions in humans (LS-1) reported by Koh et al using conventional CT 19 .…”

Systemic immune-inflammation index (SII): A More Promising Inflammation-Based Prognostic Marker for Patients with synchronic colorectal peritoneal carcinomatosis

“…Franko [4] analyzed the database of Analysis and Research in Cancers of the Digestive System (ARCAD) and reported that patients with isolated peritoneal metastasis had worse median survival times (16.3 months) than those with liver (19.1 months), lung (24.6 months), or lymph node (19.4 months) only respectively. Moreover the tumor biological behavior, survival outcome and therapeutic effect of isolated PM origined from CRC significantly differed from other subsets of metastatic colorectal cancer (mCRC) [6,7] . It was important to find out appropriate prognostic markers to predict survival outcome and guide surgeons to choose optimal treatment strategies for SCRPC patients.…”

<p>The Validity of Registered Synchronous Peritoneal Metastases from Colorectal Cancer in the Danish Medical Registries</p>

“…For example, there is a large variability in the sensitivity of the radiological imaging ranging from CT scans, PET/CT and MRI and the variability is dependent on the anatomical site and size of the peritoneal metastases. 10 Patients registered with primary colorectal cancer n= 10,336…”

“…The sensitivity of a PM diagnosis is based on preoperative radiological assessment such as computer tomography (CT) scans, and has been reported with a great variance from 11% to 96%. 10 Currently, no radiological imaging is superior to an intra-operative assessment of the peritoneal cavity. 11 Registries contain large comprehensive data, and the registration of S-PM enables clinicians and researchers to monitor prevalence and incidence along with treatment methods, mortality rates and the prognosis.…”