Colorectal Cancer

 

COLORECTAL CANCER

Shourya Mukherjee, Dr. Lopamudra Das Roy

Published 2021

@BreastCancerHub, All Rights Reserved

Abstract

Colorectal cancer is one of the most prevalent cancers in the world. Incidence and mortality were found to be strongly associated with developing countries more so than developed countries. Further corroborating previous research, factors including race, fitness, and family history continue to affect colorectal cancer risk. The highly established treatment regimens of CAPOX and FOLFOX (mFOLFOX6) show that oxaliplatin-based regimens are far more effective across all stages in low-risk, average-risk, and high-risk patients.

Introduction

Colorectal cancer (CRC) is the third most common cancer diagnosed in both men and women, covering 8% of all cancer cases in men and women each. In 2021, a total of 104,270 cases of colon cancer, while a total of 45,230 cases were reported for rectum cancer [1]. Colon cancer typically occurs when a cell's DNA is damaged so that the cell divides at an abnormal rate. This abnormal growth allows the formation of polyps and eventually malignant tumors, which can invade normal tissue and impair body function [2]. 

Aim

The aim of this research is to review the existing literature on CRC, focusing primarily on incidence and mortality rates, risk factors, diagnosis, and the efficacy of different treatments, primarily focusing on the adjuvant chemotherapy for the different stages of CRC. 

Methods

The primary database used to accumulate sources was PubMed, although the National Center for Biotechnology Information (NCBI) and ScienceDirect were occasionally used. Additional resources include the information available through Mayo Clinic, The American Cancer Society, and The John Hopkins Hospital.

Discussion

Incidence and Mortality 

CRC contributes to about 60% of all deaths in countries with a high human development index (HDI), suggesting that CRC is a primary concern in developed countries3. In a study conducted by Moura et al. on the incidence and mortality rates of colorectal cancer in a Brazilian city [3, 4]. 0.5% of patients were male and 59.5% were female. Left colorectal cancer (LCRC) was far more common than Right colorectal cancer (RCRC) in both males and females. Over a period from 1996 to 2015, both male and female incidence rates showed constant growth, however, mortality rate trends were fairly stable. Several other countries share this trend of increasing incidence rates and mortality rates leveling off from 1960 to 2010, including Poland, Costa Rica, Latvia, and Lithuania. Other countries like Denmark, Finland, Ireland, and Italy even have to decrease mortality rates [4]. Countries with increasing incidence rates and increasing mortality rates tend to be more developed. 

Risk Factors and Screening

Age, genetics, race, and gender are all risk factors that cannot be avoidable. On the other hand, diet, physical activity, weight, smoking, low calcium content, high salt intake, and exposure to occupational hazards are considered risk factors that are within the patient's control [2, 5, 6, 7, 8]. 

A family history of CRC is a significant risk factor [2] and specific guidelines are in place to ensure early diagnosis for patients with 1st or 2nd-degree relatives with CRC. In a study conducted on 2,473 CRC cases10, 62.2% of patients diagnosed could have been recommended screening prior to age 40 according to ACS guidelines, which recommend beginning initial screening 10 years prior to the youngest 1st-degree relative’s diagnosis. Out of 614 individuals diagnosed with colorectal cancer from ages 40 to 49, 149 (24%) had a first-degree relative with CRC at a younger age, suggesting that early screening could have resulted in an earlier diagnosis. If the recommended age of screening initiation had been applied to just 1 in 4 cases with a history of early-onset CRC (EOCRC), 98% of cancer could have been detected earlier [10].

Race can sometimes be a risk factor2, and can sometimes warrant early screening initiation11. For example, CRC incidence is higher in African Americans than in non-Hispanic whites, which puts African Americans at higher risk of CRC5. Racial minorities are generally diagnosed with CRC at earlier ages in more advanced stages when compared with non-Hispanic Whites. In ages < 50, African Americans, Hispanics, and Asians/Pacific Islanders were first diagnosed in more advanced stages (III/IV) compared to non-Hispanic Whites10. According to statistics from The American Cancer Society [11], CRC incidence was highest in the non-Hispanic Black population at 43.6 cases per 100,000. In comparison, the non-Hispanic White population had an incidence of 36.6 cases per 100,000, while the Asian/Pacific Islander, American Indian, and Hispanic populations had 29.2, 42.3, and 32.9 cases per 100,000. Although the gender disparity was minute in most groups, non-Hispanic Black males had 51.6 cases per 100,000, while females had only 37.9 cases per 100,000, which shows a significant risk in African American males in particular. As a result, although the US Preventive Services Task Force recommends beginning screening at 50 years old, individuals that face higher CRC risk are recommended earlier screening. Even though African Americans are grouped into the high-risk category, people of different races may also be eligible for earlier screening initiation.

The patient’s level of physical activity plays a huge role in their risk of getting CRC as well as their prognosis after the diagnosis. Physical activity (PA) levels are observed to be inversely associated with risk of colon cancer [12, 13]. In fact, even a moderate level of PA shows a significantly reduced risk of digestive system cancers, when compared to low PA13. PA also has post-diagnostic benefits [14, 15, 16, 17]. In one study14, Patients that reported 0-10 MET-hours/week experienced increased survival rates over the next 8 years. In a separate study of 536 diagnosed with CRC14, the impact of exercise was most strongly felt by participants in stage II and stage III. The literature showed that the ideal level of physical activity was 17.5 to 35 MET-hours/week, which reduced mortality by up to 40%16. Interestingly, even though participants with greater body fat percentage, waist circumference, and weight had lower survival rates, BMI did not have as significant an impact on mortality [14, 15, 16, 17]. 

Figure 1. Dotted lines show patients that exercised, whereas filled lines show patients that did not exercise significantly. Stage II and Stage III patients experienced the largest benefit from exercise [14].

As for risk factors within the patient’s control, diet has been proven to have similar benefits to the patient’s prognosis. Although the presence of BRAF mutations in CRC was not associated with dietary factors like red meat, processed meat, white meat, white fish, and fatty fish [17], higher intake of fruit, vegetables, and fiber have been associated with decreased CRC risk as well as decreased risk of BRAF-wildtype and KRAS-wildtype mutations [18]. In a similar vein, smoking is strongly associated with micro-satellite high (MSI) CRC cases and there exists a strong link between smoking and BRAF mutations [19].

The current screening guidelines recommend that average-risk individuals begin screening between the ages 50 to 75 [13]. A common and highly recommended screening modality is a colonoscopy12, 13. A colonoscopy uses a long tube with a video camera to locate unusual areas of the colon, and can be used to identify polyps, and small clumps of primitive tumor cells. If polyps are detected, the patient and 1st and 2nd-degree relatives are at higher long-term risk of CRC6, [13], but the colonoscopy allows the doctor to pass surgical tools and remove polyps during the operation. The screening guidelines for these patients suggest that CRC screening should be initiated at an age of 40 or 10 years before the youngest affected relative for individuals with CRC of advanced polyp in a 1st-degree relative at age < 60 or in 2 first-degree relatives at any age. If the patient has exactly 1 first-degree relative with CRC or advanced polyp, they should begin screening 10 years before the youngest affected relative or at 40 years, and then resume average risk screening [13]. Doctors may also use blood tests to monitor the health of the colon, liver, and kidneys, but more importantly, to monitor carcinoembryonic antigens (CEA), a chemical that is a known prognostic factor for early CRC12. Aside from a colonoscopy and FIT, other screening options include flexible sigmoidoscopy, multitarget stool DNA test, CT colonography, or colon capsule [13].

Treatments

Adjuvant chemotherapy is a typical postoperative treatment plan that can be supplemented with other treatments. Oxaliplatin-based chemotherapy is a standard treatment for patients with stage III colon cancer and the two main oxaliplatin-based regimens are CAPOX and FOLFOX (currently mFOLFOX6) [20, 21, 22]. However, the benefit of adjuvant chemotherapy in stage II colon cancer remains controversial [22, 23, 24] . It is sometimes given to patients with metastatic CRC (mCRC) in the form of CAPOX, CAPIRI, and FOLFOX [23, 25, 26]. The positive effects of oxaliplatin are well documented in the literature. When low risk stage II colon cancer patients were treated with fluoropyrimidines alone, no significant benefit was observed in the > 70 years old group, the 65 - 75 years old group, the 60 - 65 years old group, and the < 60 years old group. However, the addition of oxaliplatin improved overall survival (OS) and disease free survival (DFS) across all age groups [24, 27,  28, 29, 30]. 

Conclusion

A patient’s family history, race, level of physical activity, and diet are risk factors that can affect the patient’s chance of a diagnosis and also affect the patient’s prognosis after diagnosis. The recommended screening guidelines favor colonoscopy for its ability to detect tumor development and polyp formation early. High-risk patients are recommended for earlier screening initiation than average-risk patients. Even though colonoscopy is the preferred screening option, other options exist and can be conditionally recommended to specific patients. Though studies comparing CAPOX and mFOLFOX6 are sparse, the prospects of both treatments are promising for stage III patients. Metastatic CRC patients can also benefit from adjuvant chemotherapy regimens in the form of CAPOX, CAPIRI, and FOLFOX. Overall, the literature strongly supports the positive impact of oxaliplatin-based adjuvant chemotherapy regimens on overall survival and disease-free survival of patients.

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