Colon Cancer

The colon makes up most of the large intestine and connects the small intestine to the rectum. It plays an important role in absorbing water and forming stool.

Most colon cancers are adenocarcinomas that arise from glandular cells in the colon lining. Some develop gradually from adenomatous polyps or other precancerous lesions, although not every polyp becomes cancer and not every colon cancer has an identifiable polyp stage.

Colon cancer develops through the accumulation of molecular changes over time. Different tumors may follow different biologic pathways, including chromosomal instability, mismatch repair deficiency with microsatellite instability, and other molecular or epigenetic changes.

Right- and left-sided colon cancers can differ in symptoms, biology, and response to some treatments for advanced disease.

Colon cancer usually develops through a combination of age-related, genetic, medical, and lifestyle factors rather than from a single cause.

Risk factors include increasing age, a personal or family history of colorectal cancer or advanced adenomas, inflammatory bowel disease, inherited cancer syndromes such as Lynch syndrome and familial adenomatous polyposis, obesity, physical inactivity, smoking, heavy alcohol use, certain dietary patterns, and type 2 diabetes.

Lynch syndrome is associated with inherited abnormalities in DNA mismatch repair genes and is one of the most common hereditary colorectal cancer syndromes. Familial adenomatous polyposis is associated with inherited APC variants and can lead to the development of numerous colorectal adenomas.

• Early colon cancer may cause no symptoms.

• Possible signs and symptoms include:

• Changes in bowel habits

• Persistent diarrhea or constipation

• Blood in the stool

• Abdominal pain, bloating, or discomfort

• Unexplained anemia

• Fatigue

• Loss of appetite

• Unexplained weight loss

• Persistent changes in stool shape or bowel patterns

A tumor that significantly narrows the bowel can cause obstruction, with symptoms such as abdominal swelling, cramping pain, inability to pass stool or gas, nausea, or vomiting.

Symptoms can also vary according to tumor location. Right-sided cancers may be more likely to present with chronic blood loss or anemia, whereas left-sided tumors may more often cause changes in bowel habits or obstruction. These patterns are not absolute.

Colonoscopy with tissue biopsy is the cornerstone of colon cancer diagnosis.

Colonoscopy allows direct examination of the entire colon and enables biopsy of suspicious lesions. It can also identify and remove some precancerous polyps.

After diagnosis, additional tests are used for staging and treatment planning.

Contrast-enhanced CT of the chest, abdomen, and pelvis is commonly used to evaluate the primary tumor, regional lymph nodes, and distant metastases, particularly in the liver and lungs.

CEA can be measured before treatment and used as an additional marker during follow-up, but it cannot diagnose colon cancer by itself.

MMR/MSI testing is important for colorectal cancers because it can help identify patients who may have Lynch syndrome and can influence both adjuvant and metastatic treatment decisions.

For metastatic disease, molecular testing commonly includes RAS and BRAF, with additional testing for biomarkers such as HER2 and KRAS G12C in appropriate patients.

Staging

Colon cancer is primarily staged using the AJCC TNM system.

T describes how deeply the primary tumor has grown through the bowel wall or into nearby structures. N describes regional lymph node involvement. M indicates distant metastases.

These factors are combined into stages I through IV.

Treatment decisions, however, depend on more than stage alone. In stage II and III disease, factors such as tumor depth, lymph node findings, bowel obstruction or perforation, histologic grade, lymphovascular invasion, and MMR/MSI status can also influence recurrence risk and treatment planning.

Treatment for colon cancer depends on disease stage, tumor location, pathologic and molecular features, presence of distant metastasis, and the patient's overall physical condition.

Unlike rectal cancer, colon cancer generally does not require routine pelvic radiotherapy; for localized disease, treatment mainly centers on surgery and postoperative adjuvant chemotherapy.

Very Early Colon Cancer

Some very early colon cancers arising within polyps can be completely treated by endoscopic removal.

Whether additional surgery is needed depends on pathology findings such as depth of invasion, resection margins, tumor differentiation, lymphovascular invasion, and other high-risk features.

If the risk of lymph node involvement is considered significant, formal colon resection with regional lymph node removal is generally recommended.

Surgery for Localized Colon Cancer

Surgery is the main treatment for most localized colon cancers.

The operation generally removes the segment of colon containing the tumor together with the associated regional lymph nodes. The remaining ends of the bowel are reconnected when this can be done safely.

The extent of surgery depends on tumor location and may include right colectomy, left colectomy, sigmoid colectomy, or other segmental procedures.

Many operations can be performed laparoscopically or with robotic assistance. A permanent stoma is not required for most elective colon cancer surgeries.

Stage I Colon Cancer

Stage I colon cancer is generally treated with surgery.

Patients who undergo adequate curative resection usually do not require routine postoperative chemotherapy and move into surveillance.

Selected very early cancers confined to a polyp may be adequately treated by complete endoscopic removal when favorable pathology criteria are met.

Stage II Colon Cancer

Not every patient with stage II colon cancer needs chemotherapy after surgery.

Patients with lower-risk disease may undergo surveillance alone following adequate resection.

Adjuvant chemotherapy may be considered when higher-risk features are present, such as T4 disease, bowel obstruction or perforation, inadequate lymph node sampling, poor differentiation, or lymphovascular or perineural invasion.

MMR/MSI status is also important because dMMR/MSI-H stage II tumors have distinct biology and may derive different benefit from fluoropyrimidine-based adjuvant chemotherapy.

Stage III Colon Cancer

Stage III colon cancer involves regional lymph nodes, and standard treatment generally includes curative surgery followed by adjuvant chemotherapy.

Common regimens include oxaliplatin-containing combinations such as FOLFOX or CAPOX.

The duration of chemotherapy may vary according to recurrence risk, regimen, tolerance, age, and overall health rather than being identical for every patient.

Metastatic Colon Cancer

When colon cancer has spread to distant organs, the first question is whether the metastatic disease can be completely removed rather than assuming that all stage IV disease is treated only with medication.

The liver and lungs are common metastatic sites.

Selected patients with resectable metastases may undergo surgery or other local treatments combined with systemic therapy and may achieve long-term disease control. Some initially unresectable liver metastases may become resectable after systemic therapy.

For disease that cannot be treated with curative local therapy, systemic treatment is the main approach.

Molecular Testing and Targeted Therapy

Molecular testing is increasingly important in metastatic colon cancer.

Key biomarkers include RAS, BRAF, MMR/MSI, and, in selected patients, HER2 and KRAS G12C.

Patients with RAS wild-type disease, particularly left-sided primary tumors, may benefit from anti-EGFR therapy such as cetuximab or panitumumab.

For BRAF V600E–mutated metastatic colorectal cancer, targeted treatment with encorafenib plus cetuximab is an established option in appropriate settings.

HER2-targeted therapy may be considered for selected HER2-positive tumors.

For previously treated KRAS G12C–mutated colorectal cancer, combinations of a KRAS G12C inhibitor with an EGFR inhibitor have also entered the treatment landscape.

Immunotherapy

Immunotherapy is guided primarily by MMR/MSI status rather than simply by whether colon cancer is advanced.

For metastatic dMMR/MSI-H colorectal cancer, immune checkpoint inhibitors can be highly effective.

Pembrolizumab is an established first-line option for selected patients with treatment-naïve dMMR/MSI-H metastatic colorectal cancer. In KEYNOTE-177, it significantly improved progression-free survival compared with chemotherapy.

Nivolumab plus ipilimumab is another immune-based option in appropriate settings.

For the much more common MSS/pMMR tumors, single-agent checkpoint inhibition generally has limited

Radiation Therapy

Radiation therapy has a much smaller role in colon cancer than in rectal cancer.

Because the colon is located within the abdomen and is relatively mobile, routine preoperative or postoperative radiation is generally not part of standard treatment for localized colon cancer.

Radiation may be used selectively for unresectable local disease, local recurrence, bone metastases, bleeding, pain, or other situations requiring local symptom control.

Supportive Care

Supportive care can be provided throughout the entire course of colon cancer treatment.

Patients may need management of anemia, pain, nausea, diarrhea, constipation, nutritional problems, or treatment-related side effects.

When bowel obstruction occurs, treatment may include surgery, a temporary or permanent stoma, endoscopic stenting, or other approaches depending on the location of the obstruction and overall treatment plan.

Palliative care can be provided together with active anticancer treatment.