Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies.

Andreas Koulouris,Maria Tzardi,Dimitrios Mavroudis,John Souglakos,Christos Tsagkaris,Maria Sfakianaki,Evangelos Xynos,Maria Trypaki,Ippokratis Messaritakis,Nikolaos Gouvas,Elias Athanasakis,Manousos Christodoulakis,Vasiliki Spyrou

doi:10.3390/cancers13143522

Abstract

Simple SummaryCRC recurrence remains a great barrier in the disease management. Metastatic disease is a highly lethal malignancy. Novel biomarkers are urgently needed to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk, thus serving as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading to appropriate stratification policies, and to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on CTCs and, even more on ctDNA, seem to pave the way to a promising, minimally invasive, and life-saving monitoring, supporting personalized treatment and favoring patients’ quality of life.Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy, although considerable progress has resulted from molecular alterations in guiding optimal use of available treatments. CRC recurrence remains a great barrier in the disease management. Hence, the spotlight turns to newly mapped fields concerning recurrence risk factors in patients with resectable CRC with a focus on genetic mutations, microbiota remodeling and liquid biopsies. There is an urgent need for novel biomarkers to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk (RR) and, thus, be used both as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading not only to the appropriate stratification policies, but also to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients’ quality of life, as well.

Highlights

Colorectal cancer (CRC) recurrence is a major concern, whose likelihood appears to increase proportionally to the disease grading on diagnosis
Most available biomarkers are not recommended for use in the daily clinical practice
Such oncogene mutations predict resistance to anti-EGFR therapy in metastatic CRC, whereas microsatellite instability (MSI) is used as a prognostic marker in stage II disease and as a predictive marker for the effectiveness of anti-PDL1/PD1 antibodies in the metastatic setting [126]

Summary

Introduction

Colorectal cancer (CRC) recurrence is a major concern, whose likelihood appears to increase proportionally to the disease grading on diagnosis. 4–33% of patients undergoing CRC surgical resection will eventually relapse [1]. In a recent population study in the US, the recurrence rate ranged from 5 to 6% in stage II colon cancer, 9.4–10.5% in stage II rectal cancer, and 14.6–17.7% in stage III CRC [2]. Several clinical and pathological factors offer a potential prognostic or predictive value, after colectomy. All these factors have been investigated in retrospective studies of population cohorts or posthoc subgroup analyses of randomized trials. The quality of surgery was not assessed in any of these studies, it has been thoroughly documented that the complete mesocolic excision (CME) is of paramount importance

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