Early stage colon cancer: Current treatment standards, evolving paradigms, and future directions

Abstract

Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies. The majority of patients with colon cancer are diagnosed at an early stage (stages I to III), which provides an opportunity for cure. The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients, which is directed at the eradication of minimal residual disease to achieve a cure. Surgery alone is curative for the vast majority of colon cancer patients. Currently, surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement. Adjuvant chemotherapy is recommended for all patients with stage III colon cancer, while the benefit in stage II patients is not unequivocally established despite several large clinical trials. Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques, strategies to limit treatment-related toxicities, precise patient selection for adjuvant therapy, utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology. In this review, we will discuss the current standard treatment, evolving treatment paradigms, and the emerging biomarkers, that will likely help improve patient selection and personalization of therapy leading to superior outcomes.

PD-L1 as a Prognostic Factor in Early-Stage Colon Carcinoma within the Immunohistochemical Molecular Subtype Classification

“…Patients with dMMR express significantly higher levels of PD-L1 in the early stages [ 26 , 47 , 48 , 65 , 66 ], which is consistent with the findings of our study ( p = 0.043 for PD-L1–L and p < 0.001 for PD-L1–H). With respect to survival, patients in the CMS1 group, defined by dMMR, have the best prognosis in early-stage CRC [ 2 , 29 , 67 , 68 ] independent of the degree of PD-L1 expression. Further, the value of PD-L1 expression as an immunohistochemical biomarker of good prognosis when assessed in immune cells has been suggested by several studies and meta-analyses [ 33 , 47 , 63 , 69 ].…”

“…As mentioned previously, CMS1 and CMS4 show very different intrinsic biological characteristics that translate into better and worse patient prognosis, respectively, in early-stage CRC [ 2 , 67 , 68 ]; this is not so clear for CMS2 and CMS3. As noted above, CMS2 displays epithelial differentiation and strong upregulation of WNT and MYC downstream targets, and CMS3 is characterized by multiple metabolism signatures.…”

“…As noted above, CMS2 displays epithelial differentiation and strong upregulation of WNT and MYC downstream targets, and CMS3 is characterized by multiple metabolism signatures. However, they sometimes share these characteristics with CMS4 or with CMS1 without distinction and this may be the reason for their unclear or intermediate prognosis [ 68 ]. For example, CMS2 shares with CMS4 a high frequency of somatic copy-number alterations and WNT/MYC pathways, and shares with CMS1 PD-1 activation and immune cell infiltration, whereas CMS3 shares with CMS4 higher KRAS mutation rates and sugar metabolic signatures, and shares with CMS1 a hypermutated profile and caspase pathways [ 3 , 19 , 75 ].…”

“…Adjuvant chemotherapy in stage II and stage III CC patients remains controversial. For stage II despite several randomized trials [ 76 , 77 ], there is still a need for robust evidence concerning the addition of adjuvant chemotherapy for all patients [ 68 ]. For stage III, some studies have been able to establish a basis for treatment decisions [ 56 , 78 , 79 ].…”

SPOCK1 promotes the proliferation and migration of colon cancer cells by regulating the NF-κB pathway and inducing EMT

“…2 surgical techniques and systemic treatment, the 5-year survival rate of CRC patients is relatively low [2,3]. Most patients with CRC are diagnosed in an intermediate or late stage and have a poor prognosis [3].…”