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About Colorectal Cancer

Медицинская проверка: Renu Meena, B.Pharm
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Colorectal Cancer: Symptoms, Stages, Causes, Screening & Treatment

Colorectal cancer is a malignancy that develops in the tissues of the colon or the rectum. It is the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths worldwide. While it has historically been seen most often in older adults, cases among individuals under age 50 have risen steadily over recent decades.
Most colorectal cancers begin as small, non-cancerous growths called adenomatous polyps. Over a period of 7 to 15 years, some of these polyps can accumulate cellular and genetic changes that turn them into invasive cancer. Because of this slow progression, screening tests such as colonoscopies can detect and remove polyps before they ever become malignant.
When colorectal cancer is caught early, five-year survival rates exceed 90%. Even in cases where cancer has spread to the liver or lungs, modern surgical techniques, targeted drugs, and immunotherapies provide effective ways to control the disease and improve survival.
This comprehensive guide covers colorectal anatomy, early warning signs, causes, screening methods, stages, and treatment pathways.

Key Facts at a Glance

  • Common Age Group: Most commonly diagnosed in adults aged 50 and older, with increasing rates in adults aged 20 to 49.
  • Gender Impact: Affects both men and women, with slightly higher rates in men.
  • Primary Sites: Right colon (cecum, ascending colon), left colon (descending, sigmoid colon), and rectum.
  • Main Cancer Type: Adenocarcinoma (originating in glandular cells that line the inner bowel wall), accounting for roughly 95% of cases.
  • Key Biomarkers: Microsatellite Instability (MSI-H / dMMR), KRAS, NRAS, BRAF V600E, and HER2 status.
  • Gold Standard Test: Colonoscopy with direct polyp removal and biopsy.
  • Main Treatments: Surgical resection (colectomy or proctectomy), chemotherapy, radiation therapy, targeted therapies, and immunotherapy.

What Is Colorectal Cancer? Anatomy and Bowel Structure

The large intestine forms the final part of the digestive tract, measuring about 1.5 meters in length. It includes the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum, and anal canal. Its main functions are absorbing water and salts from digested food and storing solid waste before it is eliminated.
The wall of the large intestine is made up of four distinct layers:
  1. Mucosa: The innermost layer lined with glandular epithelial cells that produce mucus. Cancer starts here.
  2. Submucosa: A layer of connective tissue beneath the mucosa containing blood vessels, nerves, and lymphatic channels. When abnormal cells break into this layer, the tumor is considered an invasive cancer capable of spreading.
  3. Muscularis Propria: A thick layer of muscle that contracts to move waste through the bowel.
  4. Serosa: The outer protective layer covering most of the colon. The lower two-thirds of the rectum does not have a serosa, and is instead surrounded by a fatty tissue layer containing blood vessels and lymph nodes called the mesorectum.

How Polyps Turn Into Cancer: Biological Pathways

Colorectal cancer generally develops through gradual changes in the cells lining the bowel:

1. The Classic Polyp-to-Cancer Pathway

Most cases follow a predictable genetic sequence. It often begins with the loss or alteration of the APC tumor suppressor gene, causing normal cells to multiply and form a benign polyp. Over time, further changes in other genes—such as KRAS and TP53—cause the polyp to grow larger, develop high-grade dysplasia, and eventually break through the inner wall as an invasive cancer.

2. The Microsatellite Instability (MSI) Pathway

About 15% of colorectal cancers develop due to defects in DNA Mismatch Repair (MMR) proteins. These repair proteins normally fix small mistakes that occur when cells copy their DNA. When they fail, errors accumulate rapidly, producing tumors with a high number of mutations known as MSI-High (dMMR) tumors. These cancers are common in people with Lynch syndrome, but can also occur spontaneously. Because these tumors display many foreign markers, they respond very well to modern immunotherapy medications.

3. The Serrated Pathway

Some cancers develop from flat, saw-toothed growths called sessile serrated polyps, commonly located on the right side of the colon. These are frequently linked to changes in the BRAF gene and chemical modifications called hypermethylation, which turn off protective repair genes.

Symptoms of Colorectal Cancer

Colorectal cancer often causes no symptoms in its earliest stages. As tumors grow, symptoms can vary significantly depending on where the tumor is located in the bowel.

Symptoms of Right-Sided (Ascending Colon) Cancer

The right side of the colon has a wider space, and stool is still mostly liquid. Because waste passes through easily, tumors can grow quite large without causing bowel blockages. Common signs include:
  • Unexplained iron deficiency anemia resulting from slow, hidden microscopic blood loss.
  • Persistent fatigue, physical weakness, and shortness of breath during routine activity.
  • Dark, tarry, or maroon-colored stools.
  • A firm, painless mass felt in the lower right side of the abdomen.

Symptoms of Left-Sided (Descending Colon) Cancer

The left side of the colon is narrower, and stool is solid. Tumors here tend to encircle the bowel, causing mechanical narrowing:
  • A noticeable, lasting change in bowel habits, such as new constipation, diarrhea, or a feeling that your bowel patterns have shifted for more than a few weeks.
  • Narrowed stools, often described as ribbon-like or pencil-thin.
  • Bright red or dark red blood visible on or mixed into the stool.
  • Cramping abdominal pain or bloating after eating.

Symptoms of Rectal Cancer

The rectum is the final holding chamber for stool:
  • Bright red blood during or after bowel movements, frequently mistaken for hemorrhoids.
  • Tenesmus, which is a persistent, uncomfortable urge to have a bowel movement even when the bowel is completely empty.
  • Deep pelvic, tailbone, or lower back discomfort.

Signs of Advanced Disease

  • Complete bowel blockage causing severe abdominal swelling, inability to pass gas or stool, and vomiting.
  • Unexplained weight loss and loss of appetite.
  • Jaundice (yellowing of the skin and eyes) or right upper belly pain if cancer spreads to the liver.
  • Persistent cough or shortness of breath if cancer spreads to the lungs.

Causes and Risk Factors

A combination of lifestyle habits, family history, and genetic predispositions influences the risk of developing colorectal cancer:

1. Modifiable Lifestyle Factors

  • Dietary Choices: Diets high in red meat (beef, pork, lamb) and processed meats (sausages, hot dogs, bacon) increase risk. Low intake of dietary fiber from fruits, vegetables, and whole grains slows bowel transit time and increases contact with waste toxins.
  • Physical Inactivity and Excess Weight: Carrying excess body weight around the abdomen and living a sedentary lifestyle lead to chronic inflammation and higher insulin levels, both of which encourage cell growth.
  • Smoking and Tobacco Use: Carcinogens from tobacco smoke are swallowed or carried through the bloodstream, accelerating the growth of bowel polyps.
  • Alcohol Intake: Moderate to heavy alcohol consumption irritates bowel cells and interferes with normal folate and nutrient metabolism.

2. Medical Conditions

  • Inflammatory Bowel Disease (IBD): Long-standing ulcerative colitis or Crohn’s colitis causes chronic inflammation that damages cells over decades. Risk begins to rise significantly about 8 to 10 years after diagnosis, requiring regular colonoscopies with multiple tissue checks.
  • Type 2 Diabetes: Individuals with type 2 diabetes share common metabolic risk factors and show higher rates of colorectal cancer.

3. Family History and Inherited Syndromes

  • Family History: Having a parent, sibling, or child who has had colorectal cancer doubles your risk. The risk is higher if multiple relatives are affected or if a relative was diagnosed before age 50.
  • Lynch Syndrome: The most common inherited condition, accounting for 3% to 5% of all cases. Caused by inherited mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2), it carries a high lifetime risk of early-onset colorectal and uterine cancers.
  • Familial Adenomatous Polyposis (FAP): A rare genetic condition caused by changes in the APC gene. Affected individuals develop hundreds to thousands of polyps starting in their teens, with near certainty of developing cancer by age 40 unless preventive surgery is performed.

Screening Methods for Early Detection

Screening allows doctors to find and remove polyps before they turn into cancer, or to discover cancers at an early, curable stage. Major guidelines recommend that adults at average risk begin regular screening at age 45 and continue through age 75.

Common Screening Tests

  1. Optical Colonoscopy (Every 10 Years): The primary screening and diagnostic tool. A doctor uses a thin, flexible tube with a camera to examine the entire colon and rectum. If polyps are seen, they can be removed immediately during the procedure, making colonoscopy both a detection test and a preventive treatment.
  2. Fecal Immunochemical Test (FIT, Done Annually): A convenient at-home stool test that checks for hidden human blood using specific antibodies. It requires no dietary restrictions. If the test comes back positive, a colonoscopy must be performed promptly to find the source.
  3. Stool DNA-FIT Test (Every 3 Years): An at-home test that combines a check for microscopic blood with laboratory checks for altered DNA markers shed by polyps or cancers into the stool. A positive result requires a follow-up colonoscopy.
  4. Flexible Sigmoidoscopy (Every 5 Years): Examines only the rectum and lower colon. It does not evaluate the upper, right side of the large intestine.
  5. CT Colonography or Virtual Colonoscopy (Every 5 Years): A specialized CT scan that creates 3D pictures of the inside of the bowel. If polyps are spotted, a regular colonoscopy is still needed to remove them.

How Colorectal Cancer Is Diagnosed and Staged

When a patient has symptoms or an abnormal screening result, doctors perform a series of tests to confirm the diagnosis and determine how far the cancer has progressed:

1. Tissue Biopsy

A sample of tissue taken during a colonoscopy is examined by a pathologist under a microscope to confirm adenocarcinoma and determine the grade of the tumor cells.

2. Blood Tests

  • Complete Blood Count: Checks for anemia caused by hidden bleeding.
  • Liver and Kidney Function Tests: Assesses general health and organ performance before treatment begins.
  • Carcinoembryonic Antigen (CEA): A protein marker in the blood. While not used for general screening, baseline CEA levels are checked before surgery and monitored regularly afterward. A rising CEA level after treatment is often the first sign that cancer may be returning.

3. Imaging Scans

  • Chest, Abdomen, and Pelvis CT Scan: Provides detailed cross-sectional views to check whether cancer has spread to lymph nodes, the liver, lungs, or peritoneal cavity.
  • High-Resolution Pelvic MRI (For Rectal Cancer): Essential for all rectal cancers to determine how deep the tumor extends into pelvic fat, how close it is to the surrounding mesorectal fascia, and whether nearby lymph nodes are enlarged.

4. Molecular Biomarker Testing

Every newly diagnosed colorectal cancer should have biomarker testing performed on biopsy tissue:
  • MSI / MMR Status: Identifies Lynch syndrome and determines whether the patient is a candidate for immunotherapy.
  • KRAS and NRAS Mutations: Predicts whether the cancer will respond to targeted anti-EGFR medicines like cetuximab or panitumumab. Tumors with RAS mutations do not benefit from anti-EGFR therapies.
  • BRAF V600E Mutation: Identifies a more aggressive form of cancer that benefits from specific targeted drug combinations.
  • HER2 Status: Identifies tumors that can be treated with HER2-targeted therapies.

The Stages of Colorectal Cancer

Colorectal cancer is staged using the TNM system, which looks at how deep the tumor has grown (T), whether lymph nodes have cancer cells (N), and whether the cancer has spread to distant organs (M):
  • Stage 0 (Carcinoma in Situ): Abnormal cells are found only in the innermost layer (mucosa). Removing the polyp or lesion during a colonoscopy is usually the only treatment required.
  • Stage I: The tumor has grown into the submucosa or muscular wall of the bowel, but has not reached the outer layer and has not spread to lymph nodes. Cured with surgery alone in more than 90% of cases.
  • Stage II: The tumor has grown through the muscular wall and may have reached or pierced the outer covering of the bowel, but has not spread to nearby lymph nodes. Most patients are treated with surgery; chemotherapy is added for patients with high-risk features.
  • Stage III: Cancer cells have spread to nearby regional lymph nodes, regardless of how deep the main tumor has grown into the bowel wall. Standard treatment requires surgery followed by several months of adjuvant chemotherapy.
  • Stage IV: Cancer has spread through the bloodstream or lymphatic system to distant organs, most commonly the liver, lungs, or the lining of the abdomen (peritoneum). Treatment involves systemic chemotherapy, targeted therapies, immunotherapy, and in selected cases, surgical removal of isolated metastases.

Treatment Approaches for Colon Cancer

Treatment plans are determined by a multidisciplinary team including surgeons, medical oncologists, and gastroenterologists:

1. Surgical Colectomy

Surgery is the primary treatment for colon cancer:
  • Partial Colectomy: The surgeon removes the segment of the colon containing the tumor, along with a healthy border of bowel on either side.
  • Lymph Node Removal: Surrounding fatty tissue containing regional blood vessels and at least 12 lymph nodes is removed along with the bowel to ensure accurate staging.
  • Restoring Bowel Continuity: The healthy ends of the bowel are reconnected (anastomosis). In emergencies involving bowel obstruction or perforation, a temporary or permanent stoma (colostomy or ileostomy) may be created.
  • Minimally Invasive Techniques: Many colectomies are performed using laparoscopic or robotic surgery with small keyhole incisions, leading to faster recovery, less pain, and shorter hospital stays compared to open surgery.

2. Adjuvant Chemotherapy

Chemotherapy given after surgery aims to destroy microscopic cancer cells that may have escaped into the circulation:
  • For Stage III Disease: The standard approach is a combination regimen such as FOLFOX (5-Fluorouracil, Leucovorin, and Oxaliplatin) or CAPOX (Capecitabine tablets and intravenous Oxaliplatin).
  • Duration of Treatment: Clinical trials show that for lower-risk Stage III cancers, 3 months of CAPOX provides the same disease control as 6 months of therapy, with a much lower risk of lasting nerve numbness or tingling in the hands and feet.
  • For Stage II Disease: Chemotherapy is considered on an individual basis if high-risk features are present, such as bowel perforation, bowel obstruction, or having fewer than 12 lymph nodes examined.

Treatment Approaches for Rectal Cancer

Because the rectum sits deep in the pelvis near the bladder, sexual nerves, and anal sphincter muscles, its treatment differs from colon cancer:

1. Total Mesorectal Excision (TME)

The gold standard surgical procedure for rectal cancer. The surgeon removes the rectum along with its surrounding intact envelope of fat and lymph nodes (the mesorectum). This technique protects the delicate pelvic nerves that control urinary and sexual function and minimizes the risk of local cancer recurrence.
Depending on where the tumor is located:
  • Low Anterior Resection (LAR): Performed for tumors located in the upper or middle rectum, preserving the anal sphincter so normal bowel movements remain possible.
  • Abdominoperineal Resection (APR): Required for tumors located very low in the rectum that invade or sit immediately adjacent to the sphincter muscles. The rectum, anus, and sphincter are removed, and a permanent colostomy is placed on the abdomen.

2. Total Neoadjuvant Therapy (TNT)

For locally advanced rectal cancers (Stage II or III), modern practice delivers all chemotherapy and radiation therapy before surgery:
  • Combining radiation therapy (to shrink the pelvic tumor) with systemic chemotherapy (to prevent spread elsewhere in the body) before surgery improves treatment completion rates and increases the likelihood of completely eliminating the tumor.
  • The «Watch-and-Wait» Approach: In some patients, total neoadjuvant therapy eliminates every visible trace of cancer on follow-up endoscopies, MRIs, and physical examinations. In these carefully selected cases, major surgery can sometimes be deferred under close surveillance every few months, preserving the patient’s natural bowel function.

Systemic Therapies for Advanced and Metastatic Disease

When colorectal cancer spreads to other parts of the body, medical therapies circulate through the bloodstream to treat cancer cells wherever they are located:

1. Chemotherapy Combinations

  • FOLFOX: Intravenous 5-Fluorouracil, Leucovorin, and Oxaliplatin.
  • FOLFIRI: Intravenous 5-Fluorouracil, Leucovorin, and Irinotecan.
  • CAPOX: Oral Capecitabine tablets combined with intravenous Oxaliplatin.
  • FOLFOXIRI: An intensive combination of all three drugs, used in fit patients who need rapid tumor shrinkage.

2. Targeted Biologic Therapies

  • Anti-VEGF Therapy (Bevacizumab): A monoclonal antibody that blocks blood vessel growth to the tumor, used in combination with chemotherapy regardless of genetic mutations.
  • Anti-EGFR Therapies (Cetuximab, Panitumumab): Drugs that block cell growth signals. They are effective only in tumors that have normal, non-mutated (wild-type) KRAS and NRAS genes, and work best for cancers that originated on the left side of the colon or rectum.
  • BRAF-Targeted Therapy: For tumors with a BRAF V600E mutation, the combination of encorafenib (a BRAF inhibitor) and cetuximab (an anti-EGFR drug) provides a targeted option.
  • HER2-Targeted Therapies: For tumors with extra copies of the HER2 gene, combinations such as trastuzumab with tucatinib are effective.

3. Immunotherapy

For patients with MSI-High or dMMR colorectal cancer, immune checkpoint inhibitors such as pembrolizumab or nivolumab plus ipilimumab have become the preferred first-line treatment. These drugs help the patient’s own immune cells recognize and attack cancer cells, producing long-lasting remissions with fewer side effects than conventional chemotherapy.

Treating Spread to the Liver and Lungs (Metastasectomy)

The liver is the most common site where colorectal cancer spreads because blood from the intestines drains directly to the liver through the portal vein.
In roughly 20% to 30% of patients with Stage IV cancer, the spread is limited to a few isolated spots in the liver or lungs. In these cases, combining chemotherapy with surgical removal of the metastases (liver resection or lung metastasectomy) or heat ablation (destroying tumors with microwave or radiofrequency probes) can lead to long-term survival, with up to 40% to 50% of patients living five years or longer.

Side Effects, Safe Medication Use, and Practical Home Care

Understanding potential treatment side effects helps patients manage daily routines safely:
  • Oxaliplatin and Cold Sensitivity: Oxaliplatin causes temporary nerve sensitivity triggered by cold temperatures. For 5 to 7 days after an infusion, patients should avoid cold drinks, ice, holding cold items, and breathing cold air. Wearing gloves when opening refrigerators and drinking room-temperature liquids is recommended.
  • Managing Diarrhea from Irinotecan: Irinotecan can cause delayed diarrhea starting a few days after treatment. Patients should keep over-the-counter loperamide on hand, drink plenty of water and electrolyte fluids, and contact their oncology nurse if diarrhea continues despite medication.
  • Safe Handling of Oral Capecitabine: Capecitabine tablets must be swallowed whole with water within 30 minutes after a meal. Tablets should never be crushed or cut. Family members should avoid directly touching loose tablets, using gloves or tipping them into a dosing cup.
  • Rash from Anti-EGFR Medications: Cetuximab and panitumumab commonly cause an acne-like rash on the face and chest. This is an expected sign that the drug is working. It is managed with gentle skin moisturizers, mild topical steroids, sun protection, and oral antibiotics prescribed by your oncologist.
  • Emergency Signs: Contact your care team or visit an emergency room immediately if you develop a fever of 38.0°C (100.4°F) or higher during chemotherapy, experience uncontrollable vomiting or diarrhea, have severe abdominal pain, or cannot pass gas or stool.

Everyday Habits to Lower Recurrence Risk

After completing treatment, healthy daily habits support recovery and reduce the risk of cancer returning:
  • Eat More Fiber and Whole Foods: Build meals around vegetables, beans, lentils, whole grains, nuts, and fresh fruits. Soluble and insoluble fiber support a healthy gut microbiome and regular bowel movements.
  • Cut Down on Processed and Red Meats: Limit beef, pork, and lamb, and avoid processed meats like sausages, bacon, and cold cuts. Choose fish, poultry, eggs, and plant-based proteins instead.
  • Stay Physically Active: Aim for at least 150 minutes of moderate aerobic activity (such as brisk walking or cycling) each week. Regular exercise is linked to significantly lower rates of colorectal cancer recurrence.
  • Limit Alcohol and Stop Smoking: Avoid tobacco in all forms and keep alcohol consumption to a minimum.
  • Keep Up with Follow-Up Checks: Attend all scheduled follow-up visits, which typically include blood tests for CEA every 3 to 6 months, regular CT scans, and a repeat colonoscopy one year after surgery.

Frequently Asked Questions

Can colorectal cancer be prevented completely?

Yes, in many cases. Most colorectal cancers start as non-cancerous polyps that take a decade or more to become malignant. When adults have regular screening colonoscopies starting at age 45, doctors can spot and remove these polyps during the procedure, stopping cancer from developing in the first place.

What is the most common early symptom of colorectal cancer?

Early colorectal cancer often produces no symptoms at all. When early symptoms do appear, they most commonly include a lasting change in bowel habits—such as constipation, diarrhea, or narrower stools lasting more than a few weeks—or visible red blood in the stool. On the right side of the colon, the earliest sign is often unexplained fatigue caused by hidden blood loss and low red blood cell counts (anemia).

Does a positive at-home stool test mean I have cancer?

No. A positive result on a fecal immunochemical test (FIT) or stool DNA test simply means that tiny amounts of blood or altered markers were detected in your sample. This can be caused by benign conditions like hemorrhoids, non-cancerous polyps, or minor inflammation. However, a positive stool test must always be followed up promptly with an optical colonoscopy to find the exact cause.

What is the difference between colon cancer and rectal cancer?

While both are cancers of the large intestine, they sit in different parts of the body and require different surgical and medical approaches. The colon is located in the main abdomen, surrounded by loose space, and is treated mainly with surgery followed by chemotherapy if needed. The rectum sits deep inside the narrow pelvis right next to the urinary and sexual nerves and the anal sphincter muscles. Rectal cancer has a higher risk of local recurrence and is often treated with combined chemotherapy and radiation therapy before surgery to preserve bowel control.

How often should an average-risk adult get a colonoscopy?

If your initial screening colonoscopy shows no polyps and you have no personal or family history of bowel cancer, guidelines recommend repeating the test every 10 years, starting at age 45. If pre-cancerous polyps are found and removed, your doctor will recommend a shorter follow-up interval, typically every 3 to 7 years depending on the size, number, and type of polyps removed.

Can colorectal cancer spread to other organs?

Yes. Colorectal cancer cells can travel through the bloodstream and lymphatic vessels. The most common site of distant spread is the liver, followed by the lungs and the abdominal lining (peritoneum). When spread is limited to a few isolated spots in the liver or lungs, surgery or thermal ablation can be used alongside chemotherapy to remove the metastases, offering a realistic chance of long-term cure.

What should I do if I see blood in my stool?

Any blood in your stool or on toilet paper should be checked by a doctor. While benign conditions like hemorrhoids or small anal tears are the most common causes, rectal bleeding can also be an early sign of polyps or cancer. A doctor or gastroenterologist will evaluate your symptoms and recommend an examination and a colonoscopy.

Is genetic testing necessary for every colorectal cancer patient?

Yes. Guidelines recommend that every newly diagnosed colorectal cancer tumor be tested for Mismatch Repair (MMR) proteins or Microsatellite Instability (MSI). This confirms whether the cancer might be related to Lynch syndrome (which is important for family members to know) and helps doctors choose the best medications, as MSI-High tumors respond very well to immunotherapy.
  1. National Comprehensive Cancer Network (NCCN):
    NCCN Clinical Practice Guidelines in Oncology: Colon Cancer & Rectal Cancer.
    Consensus clinical practice guidelines for staging, surgical margins, chemotherapy regimens, and follow-up care:
  2. American Society of Clinical Oncology (ASCO):
    ASCO Guidelines: Treatment of Early-Stage and Metastatic Colorectal Cancer.
    Evidence-based guidance on systemic chemotherapy, anti-EGFR therapies, and immunotherapy:
  3. European Society for Medical Oncology (ESMO):
    ESMO Clinical Practice Guidelines for Diagnosis, Treatment, and Follow-up of Colorectal Cancer.
    International recommendations covering Total Mesorectal Excision standards, rectal cancer watch-and-wait strategies, and liver metastasectomies:
  4. U.S. Multi-Society Task Force on Colorectal Cancer:
    Colorectal Cancer Screening and Post-Polypectomy Surveillance Guidelines.
    Consensus recommendations from gastroenterology societies regarding screening ages and colonoscopy intervals:
  5. World Health Organization (WHO) – International Agency for Research on Cancer (IARC):
    Global Cancer Observatory: Colorectal Cancer Statistics and Prevention Monographs.
    Global epidemiological data, dietary carcinogen classifications, and population screening benchmarks: