Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

Abstract

The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.

A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis

“…Routine imaging-based diagnosis often limits the detection of cancer due to its small size or difficulty in separating it from soft tissues, which is particularly important for diagnosing metastases and assessing response to treatment [ 115 ]. A clinical challenge important for selecting and planning an appropriate management and treatment strategy is to perform a comprehensive clinical analysis that includes the use of the most recent imaging techniques combined with the assessment of tumor biomarkers and genetic features of the tumor [ 115 ]. The detection level of most conventional imagining techniques is insufficient to detect metastases.…”

“…The detection level of most conventional imagining techniques is insufficient to detect metastases. New techniques such as diffusion-weighted MRI (DW-MRI) or fibroblast activation protein inhibitor–positron emission tomography (FAPI-PET) is prospective due to high specificity and sensitivity, also in the case of extraperitoneal lesions [ 115 , 116 , 117 , 118 ].…”

Current Opinion and Practice on Peritoneal Carcinomatosis Management: The North African Perspective

“…In the case of metastatic spreading, this can be justified using either one of the two main hypotheses whereby tumor progression can be promoted by anatomical factors such as the local spreading of tumor cells after breaching the initial site or by the "seed-and-soil" hypothesis implying the specific tropism of tumor cells circulating in the lymphatic or vascular systems to certain organs. However, unknown alternative biological routes may also exist (27)(28)(29). As such, management options also vary according to tumor origins, and whether the aim of treatment is curative or palliative.…”

Peritoneal metastasis of colorectal cancer (pmCRC): identification of predictive molecular signatures by a novel preclinical platform of matching pmCRC PDX/PD3D models

“…Colorectal cancer (CRC) is the third most frequent cancer type worldwide [ 1 ] and distant metastasis represents its most lethal attribute. About every second CRC patient develops distant metastasis [ 2 , 3 ] and about 30% as peritoneal metastasis (pmCRC) [ 4 ] associated with inferior outcome and limited treatment opportunities [ 5 , 6 ]. This defines an urgent need for applied translational research to identify and exploit new biomarkers, signatures, and molecular targets for personalized pmCRC treatment with well-characterized pre-clinical disease models.…”