Colorectal Cancer

Introduction

Colorectal cancer, often called bowel, colon, or rectal cancer, originates in the large intestine (colon and rectum). It results from abnormal, uncontrolled cell growth that can spread to other parts of the body. In many cases, it begins as a small, noncancerous polyp that gradually transforms into cancer.

Symptoms

Typical signs include:

• Blood present in the stool
• Noticeable changes in bowel habits
• Ongoing abdominal discomfort or pain
• Unexplained weight loss
• Fatigue and reduced energy levels

In older adults, constipation that worsens, thinner stool, appetite loss, or nausea and vomiting can indicate the disease. However, about half of those diagnosed may not initially show any symptoms. Rectal bleeding and anemia in individuals over 50 are considered strong indicators.

Causes and Risk Factors

Most colorectal cancers are linked to environmental and lifestyle factors, with only a small percentage tied to genetics.

Main risk factors include:

• High-fat or high-sugar diet
• Frequent intake of red or processed meat and alcohol
• Smoking and obesity
• Sedentary lifestyle
• Older age and male sex

Around 75–95% of cases occur in people without a genetic predisposition. Still, hereditary conditions like Lynch syndrome (hereditary non-polyposis colorectal cancer) and familial adenomatous polyposis (FAP) contribute to some cases, though together they account for less than 5%.

Chronic inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, raises the likelihood of cancer.

Certain infections also play a role. For instance, bacteria like Streptococcus gallolyticus and pathogenic Escherichia coli have been associated with colon tumors.

Pathogenesis

The cancer commonly develops due to changes in the Wnt signaling pathway, especially mutations in the APC gene. This gene normally prevents excessive buildup of β-catenin, but when mutated, it causes abnormal cell proliferation.

Other mutations, such as those affecting TP53 or KRAS, also drive tumor formation. Epigenetic changes—like abnormal DNA methylation or microRNA regulation—are equally important in cancer progression.

The “adenoma-to-carcinoma sequence” explains how normal colon lining changes into polyps and eventually invasive cancer through cumulative genetic and epigenetic changes.

Diagnosis

Diagnosis begins with endoscopic procedures:

• Colonoscopy or sigmoidoscopy allows visualization and biopsy.
• Larger tumors may require biopsy to confirm malignancy.

Imaging methods (CT, MRI, PET) help identify how far the cancer has spread. MRI is especially useful for rectal cancer staging and surgical planning.

Histopathology usually reveals adenocarcinoma, which makes up over 95% of cases.

Screening

Screening prevents cancer by detecting and removing polyps early. Common methods include:

• Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) every 1–2 years
• Colonoscopy every 10 years
• Sigmoidoscopy every 10 years (though it misses cancers in the right colon)

Routine screening is recommended for adults aged 45 to 75, lowered from 50 due to rising cases in younger populations. Those at high risk (family history, genetic syndromes) should begin earlier.

Treatment

Treatment depends on stage and spread:

• Surgery: Often curative for localized disease
• Chemotherapy and radiation: Used in advanced cases or after surgery
• Targeted therapy: Drugs that attack specific cancer cell mechanisms

When the cancer is limited to the colon wall, surgery offers a good chance of cure. Once it has metastasized widely, treatment focuses more on symptom management and quality of life.

Prognosis

Survival depends on stage, ability to remove the tumor, and overall health. In the United States, the five-year survival rate is about 65%. Worldwide, colorectal cancer is the third most common cancer, responsible for roughly 10% of cases. In 2018, over 1 million people were newly diagnosed, and more than half a million died, with most cases occurring in developed countries.

Prevention

An estimated half of colorectal cancers are preventable. Measures include:

• Maintaining a healthy weight
• Regular physical activity
• Eating more fiber, fruits, vegetables, and whole grains
• Reducing consumption of red and processed meats
• Avoiding smoking and excessive alcohol intake

Some evidence suggests protective effects of dairy products and vitamin D. Aspirin and other NSAIDs may reduce risk in high-risk individuals, but they are not recommended for routine use due to side effects.

Treatment of Colorectal Cancer

General Approach

Management of colorectal cancer may aim for either cure or palliation, depending on several factors: the patient’s overall health, personal preferences, and the stage of the tumor. Multidisciplinary teams usually assess suitability for surgery. When diagnosed at an early stage, surgical removal can be curative. However, in advanced cases with widespread metastasis, complete cure is unlikely, and treatment instead focuses on controlling symptoms and maintaining comfort.

Surgery

For early-stage disease, tumors may be removed during a colonoscopy using techniques such as endoscopic mucosal resection or endoscopic submucosal dissection, provided the chance of lymph node spread is low and the tumor is accessible.

For localized cancers, the preferred method is surgical resection with clear margins. This often involves a partial colectomy (or proctocolectomy for rectal cancer), in which the affected section of the bowel, surrounding mesocolon, blood supply, and draining lymph nodes are removed. This may be done either through open surgery (laparotomy) or minimally invasive laparoscopy. Afterward, the colon is usually reconnected, though in some cases a colostomy may be required.

If only a small number of metastases exist in the liver or lungs, these too may be surgically removed. Sometimes preoperative chemotherapy is used to shrink tumors before attempting resection. In cases of peritoneal carcinomatosis, aggressive cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can be attempted.

Chemotherapy

Chemotherapy may be given alongside surgery depending on the stage:

• Stage I colon cancer: Surgery alone is usually sufficient.
• Stage II colon cancer: Chemotherapy is not routinely given unless high-risk features are present, such as poorly differentiated tumors, T4 invasion, vascular spread, or inadequate lymph node sampling.
• Stage III and IV: Chemotherapy becomes an essential component.

For cancers involving lymph nodes or distant organs, drugs like fluorouracil, capecitabine, oxaliplatin, or irinotecan improve survival. Common regimens include FOLFOX, FOLFIRI, FOLFOXIRI, and CAPOX. Targeted therapies may also be used:

• Anti-angiogenic drugs such as bevacizumab block blood vessel growth.
• EGFR inhibitors like cetuximab and panitumumab are used in certain cases.

In rectal cancer, chemotherapy is often combined with radiation therapy before surgery to shrink the tumor and reduce the need for permanent colostomy.

Radiation Therapy

Radiation is used more often in rectal cancer than colon cancer, as the bowel is highly sensitive to radiation. It can be given before surgery (neoadjuvant therapy) for stage T3 and T4 rectal tumors to reduce tumor size and recurrence risk.

However, radiation can cause significant side effects, including skin irritation, bowel inflammation, and long-term pelvic complications. In anal cancer, combined chemoradiotherapy with 5-FU and mitomycin C is preferred over radiation alone, improving survival outcomes.

For patients with lung metastases from colorectal cancer, radiation therapy has also been considered in selected cases.

Immunotherapy

A subset of colorectal cancers with mismatch repair deficiency (dMMR) or microsatellite instability (MSI-H) respond well to immune checkpoint inhibitors. Drugs such as pembrolizumab and dostarlimab (anti–PD-1 antibodies) have shown promising results in clinical trials, sometimes eliminating the need for surgery or chemoradiation in early-stage rectal cancers. However, long-term outcomes remain under investigation.

Palliative Care

For advanced or incurable cases, palliative care is crucial. It focuses on relieving symptoms, reducing hospital admissions, and supporting both patients and families. Palliative procedures may include:

• Non-curative surgery to remove part of the tumor
• Bypass procedures or stent placement to relieve obstruction
• Radiation or pain management to reduce discomfort

Psychosocial Support

Beyond medical treatment, many patients face anxiety, depression, and social stigma related to colorectal cancer, especially those with stomas. Psychosocial interventions—such as counseling, support groups, or body-mind practices—help patients cope with emotional and social challenges.

Common issues include changes in body image, sexual dysfunction, incontinence, and fear of recurrence, all of which can affect quality of life.

Follow-Up Care

After treatment, regular surveillance is essential:

• Physical exams and medical history every 3–6 months for 2 years, then every 6 months up to 5 years
• Blood tests for carcinoembryonic antigen (CEA) levels in select patients
• CT scans for high-risk individuals annually for the first 3 years
• Colonoscopy at 1 year post-treatment, then at 3 years, and every 5 years if no abnormalities are found

Routine PET scans, ultrasounds, and chest X-rays are not recommended unless symptoms suggest recurrence.

Prognosis and Survival

Survival strongly depends on the cancer stage at diagnosis. Early detection offers excellent outcomes:

• Stage 0–I: Five-year survival rates of 86–100%
• Stage II: Around 70–78%
• Stage III: Around 40–67%
• Stage IV: Less than 30% (sometimes under 5% for extensive metastasis)

Although recurrence risk has decreased with modern treatments, lifestyle changes, psychosocial support, and long-term monitoring are vital for survivorship.