The overall incidence and mortality of colorectal cancer have been declining steadily during last few decades. However, the incidence rate of colorectal cancer has significantly increased over the last two decades in patients with age between 20 to 49 years.
The large intestine consists of mainly 4 regions: cecum, colon, rectum, and anal canal. The colon, which forms the major part of large intestine, is further divided into 4 main portions: ascending colon, transverse colon, descending colon, and sigmoid colon. The next about 15 cm long continuation of the colon is termed as the rectum.
Risk Factors for Colon Cancer
Prevalence of colon cancer is more in developed countries, more so in the obese population. And migration to the developed countries also increases the risk of the disease.
But for the past few years, the incidence of colon cancer is decreasing in USA and Canada, whereas it is increasing in China and Japan. Moreover, it’s incidence in the population more than 50 years of age is going down, whereas, it is increasing in young population less than 50 years of age.
- Risk of developing colorectal cancer almost doubles in an individual with a history of colorectal cancer in first-degree relatives (parents, brother, sister, or child).
- The risk further increases several folds for such individuals if the first-degree relative gets diagnosed with the disease at an age </=60 years.
Following are some examples:
- Lynch syndrome or hereditary non-polyposis colorectal cancer
- Familial adenomatous polyposis (FAP)
- Peutz-Jeghers syndrome
- Juvenile polyposis
Inflammatory Bowel Disease
- Individuals with a history of colorectal cancer, adenomatous polyps, inflammatory bowel disease (ulcerative colitis or Crohn’s disease) are generally at higher risk of developing colorectal cancer.
- Ulcerative colitis carries a risk of colorectal carcinoma 30 times greater than general population.
- Risk increases with duration of disease.
- After 30 years, risk increases to 35%.
- Crohn’s disease associated with 10-20 fold increased risk of cancer.
- Need to do surveillance in these population.
Most cases of colorectal cancer risk factors develop from non-cancerous adenomatous polyps through a process called adenoma-carcinoma sequence.
- Older age individuals are generally at increased risk of developing colorectal cancer.
- Older age is also associated with high-grade dysplasia within an adenoma, independent of size and histology.
- Tobacco/cigarette smoking, excess alcohol consumption, and
- low physical activity have been reported to increase the risk of developing colorectal cancer.
- Cigarette smoking- More than 20 pack years increases the risk of large adenoma, and more than 35 pack years increases cancer risk.
- Obesity, diabetes mellitus (especially type 2 diabetes), high waist girth are some other risk factors for colorectal cancer.
- Consumption of red and processed meat, high-calorie diet, animal fat; and low intake of fruits and vegetables, fish, legumes, dietary fibers, and vitamins have been implicated to elevate the risk of colorectal cancer.
- Alcohol consumption increases risk
- No clear cut risk with coffee or tea
- Use of certain drugs like aspirin, other nonsteroidal anti-inflammatory drugs (NSAID), hormone replacement therapy, and COX-2 inhibitors have been reported to decrease the incidence of colorectal cancer.
- Folate is protective.
- Calcium supplementation decrease new adenomas.
Signs and Symptoms of Colon Cancer
Early warning signs of colon cancer
- Changes in the bowel habit – Colonic mass may cause constipation due to the obstruction of colon that may prevent the passage of stools. It may also cause diarrhea or loose stools.
- Abdominal pain or discomfort – This may be caused due to obstuction/constipation. Other causes may be ascitis or fluid collection in peritoneal cavity, gaseous distension, or metasstasis to other abdominal organs.
- Bloating or sense of abdominal distension – It may be gaseous distension due to non-passage of flatus, or may be caused due to constipation or ascitis.
- Reddish or blackish stools – Fresh blood in stools may cause reddish discoloration, that may occur due to low lying tumor or due to excessive blood loss from tumor. Whereas, passage of clotted blood may cause blackish stools.
- Nausea and/or vomiting – Non passage of stools and/or gases may cause the sensation of nausea and/or vamiting.
- Tumors in the distal part (left-sided colon) or in the rectum are generally associated with blood in stool, altered bowel habit and/or obstructive symptoms.
- While tumors in proximal (right-sided colon) causes occult blood in stools or malena (dark tarry feces).
What are the signs of end stage colon cancer
- Ascitis or fluid collection in abdomen causing distension– Peritoneal metastasis may cause ascitis (or fluid collection in peritoneal cavity) that may lead to abdominal distension when the fluid accumulates above a vertain volume.
- Breathlessness, cough, chest discomfort – Spread of the tumor to lungs and/or pleural cavity (leading to pleural effusion) may cause difficulty in breathing, pain during inspiration, cough, etc.
- Jaundice – Yellowish discoloration of eyes and/or urine may occur as a result of tumor metastasis to the liver.
How is Colon Cancer Diagnosed?
Once someone is suspected to have colon cancer based on signs and symptoms, further investigations are needed to confirm the diagnosis and stage the disease. Some diagnostic techniques can accurately determine the extent of cancer invasion in the intestinal wall and spread of the disease to other body parts, which in turn help in selecting an appropriate treatment option.
Digital Rectal Examination
- Digital rectal examination can be done in which a doctor examines the rectum for an abnormality by inserting a lubricated, gloved finger via the anus.
- This test can provide little information about cancer within the rectum or in nearby organs. Thus, detailed investigations are required to establish the diagnosis of cancer.
Barium Enema/Double-Contrast Barium Enema (DCBE)
- In double contrast barium enema, a thick, viscous liquid containing barium (a heavy element that reflects x-rays) and the air is administered into the rectum and colon via the anus.
- Then, x-rays images are obtained for the lower abdomen where any polyps or cancer lesions are detected by the irregular barium coating.
- The test has relatively higher sensitivity for larger lesions and in symptomatic patients. It cannot be used to determine the extent of invasion or the spread of cancer to distant organs.
- Colonoscopy is a diagnostic technique which uses a colonoscope that enables to directly observe the lining of the rectum and entire colon to look for any abnormality and collect biopsy.
- Colonoscopy is one of the most important investigations which is required to confirm the disease. In this, a colonoscope is passed through the rectum into the intestine, that helps in localising the site of the tumor. We can take a biopsy from the tumor for histopathological diagnosis.
- Also we can do an endoscopic ultrasound, to assess the depth of infiltration of tumor and involvement of adjacent structures and regional lymph nodes by the tumor.
- This technique is very similar to with the only difference being the extent of the area examined during the test.
- Sigmoidoscopy helps in examining the distal part of the colon and the complete rectum.
Carcinoembryonic antigen (CEA)
- An elevated level of serum CEA may be associated with colorectal cancer, but it may be false positive or false negative in some cases.
- This can, however, be useful in assessing the efficacy of the treatment/surgery and the progression/recurrence of the disease.
- CEA is the tumor marker for colon cancer. Baseline level of CEA should be done to assess the response to treatment.
Laboratory and Imaging
- Biopsy samples contains a small piece of tissue, collected from the colonic mass with the help of a biopsy instrument.
- Imaging tests help in staging of the disease. CT scan of abdomen helps us to assess the local and distant spread of the tumor to other structures. Rarely, PET CT scan may also be required. Imaging of chest with X-ray or CT scan may also be required in some cases, depending upon the symptoms.
TNM Staging of Colon Cancer
This pouch-like structure, present at the beginning of the colon is called as caecum. This part, present on the right side of the abdomen, extending upwards from the caecum is called an ascending colon. The longest part of the colon, that extends from the right to the left side of the abdomen, is called as transverse colon. And this part, which extends downwards from transverse colon, on the left side of the abdomen, is called as descending colon. And this last part, which connects colon to the rectum and anal canal is called as sigmoid colon. These are the loops of the small intestine that occupy the central part of the abdomen. This is the cross-section from the wall of the colon, with the upper part being inside and lower part being outside of the wall. The innermost layer is epithelium, followed by this layer called as lamina propria. Outer to which lies muscularis mucosa. Then comes the submucosa. Outer to which lies the muscularis propria which is followed by a layer of pericolorectal tissue. On the outermost aspect, lies this layer which is called as serosa.
Tis – Pre-cancerous or cancer cells present only in the superficial layer (epithelium) of colorectal mucosa
T1 – Cancer extends to the lamina propria
T2 – Cancer extends to the muscular layer (muscularis propria)
T3 – Cancer extends through the muscularis propria into the pericolorectal tissues
T4a – Cancer has invaded up to the outermost serosa layer (or visceral peritoneum)
T4b – Cancer has invaded into the adjacent structures/organs like small intestine, kidneys, pancreas, or stomach.
Now we will discuss the N staging or the nodal staging for colon cancer. In this figure, you can see the draining lymph nodes for the colon. It can be called as N0, N1 or N2, depending upon the number of lymph nodes involved.
N0 – Cancer has not spread to regional lymph nodes
N1 – Cancer has spread to 1 to 3 nearby lymph nodes
N2a – Cancer has spread to 4 to 6 nearby lymph nodes.
N2b – Cancer has spread to >/=7 nearby lymph nodes.
Lastly, we will discuss the M-staging or the metastatic staging of the colon cancer. Liver is the most common site for the distant spread of the tumor from colon.
Due to the direction of vascular drainage, after liver, lungs are the second most common organs involved by metastasis.
This figure shows the spread of colon cancer to both the lungs, in form of multiple nodular deposits. And sometimes, both lungs and liver maybe involved in the metastatic spread of the disease, as we can see in this figure. The tumor may also spread to the peritoneum, in form of peritoneal deposits. It may rarely spread to one or both the ovaries. Very rarely, the tumor may also spread to the brain or bones.
M1a – Cancer has spread to one distant organ without peritoneal spread.
M1b – Cancer that has spread to >/=2 distant organs without peritoneal spread.
M1c – Cancer that has spread to peritoneum with or without other sites.
4 Stages of Colon Cancer
Based on the TNM classification described above, colon cancer may be divided into 4 stages as descibed below.
|0||Tis N0 M0|
|I||T1-2 N0 M0|
|IIA||T3 N0 M0|
|IIB||T4a N0 M0|
|IIC||T4b N0 M0|
|IIIA||T1-2 N1/1c M0|
|T1 N2a M0|
|IIIB||T3-4a N1/1c M0|
|T2-3 N2a M0|
|T1-2 N2b M0|
|IIIC||T4a N2a M0|
|T3-4a N2b M0|
|T4b N1-2 M0|
|IVA||Any T Any N M1a|
|IVB||Any T Any N M1b|
|IVC||Any T Any N M1c|
Stage 1 Colon Cancer
Stage 1 colon cancer includes cases with T1 and T2 disease, that is, disease extending upto muscularis propria.
Stage 2 Colon Cancer
In T3, cancer extends through the muscularis propria into the pericolorectal tissues.
In T4a, cancer has invaded up to the outermost serosa layer of colonic wall.
In T4a, colon cancer has invaded into the adjacent structures/organs like small intestine, kidneys, pancreas, or stomach.
A tumor present in almost any part of the colon may infiltrate into the small intestine.
Tumor in the ascending colon may infiltrate into the right kidney. And that in the descending colon may infiltrate into the left kidney. A transverse colon tumor may extend to involve pancreas. And may even extend to involve the stomach.
Stage 3 Colon Cancer
All node positive cases come under stage 3 disease. It may be N0, N1 or N2 depending upon the number of lymph nodes involved. It has been discussed above in N staging.
Stage 4 Colon Cancer
It is also called as metastatic colon cancer. When the disease spread to non-regional lymph nodes or distant sites, it is called as stage 4. It has been discussed in detail above in M staging.
Survival/Life Expectancy of Colon Cancer based on Staging
- Cancer is limited to the bladder.
- 5 year survival 90%.
- Cancer has spread to nearby structures or lymph nodes
- 5 year survival 71%.
- Cancer has spread to distant body parts like lungs, liver or bones.
- 5 year survival 14%.
Treatment of Colon Cancer
Colon cancer can be divided into 4 stages from 1 to 4. Treatment options vary depending on the stage of colon cancer along with other factors. Here, we will be discussing the treatment options depending on stage.
Stage 1 Treatment
Stage 2 Treatment
In T3, cancer extends through the muscularis propria into the pericolorectal tissues.
Stage 3 Treatment
Stage 4 Treatment
Now, we come to metastatic or stage 4 colon cancer treatment. It may present as metastasis to liver or lungs. It may also present as metastasis to both, lungs and liver. To peritoneum in the form of peritoneal or omental deposits. Very rarely, it may also spread to brain or bones. For most cases of metastatic disease, chemotherapy with/without targeted therapy is the treatment of choice.
Treatment of metastatic disease depends on whether it is resectable or non-resectable.
Non-Resectable Stage 4 Disease
Most cases of metastatic disease are treated with chemotherapy with/without targeted therapy. Immunotherapy is also an option for treatment of metastatic colon cancer.
Resectable Stage 4 Disease
In some selected cases, with limited metastasis to liver and/or lungs, tumor resection may be possible. Also in unresectable disease, it may become resectable if it responds nicely to treatment. When limited liver metastasis involves only a small part of liver, surgical resection may be tried. Similarly, if lung metastasis is localised to only a small part, that can be removed safely, resection may be done.
Other modalities like radiotherapy, surgery or bone-directed therapy, may also be used, for palliation or relief of symptom. Always remember that the treatment for metastatic colon cancer is not generally curative, so the main intent for the treatment is a prolongation of life, reduction of symptoms and improvement of the quality of life. With this, we come to the end of metastatic colon cancer treatment.
Role of Targeted Therapy
- Cetuximab and Panitumumab target epidermal growth factor receptor (EGFR) protein.
- Bevacizumab targets vascular endothelial growth factor (VEGF) receptor.
- They are generally used alone or in combination with chemotherapy for the treatment of higher stage disease.
Role of Immunotherapy
Pembrolizumab and nivolumab have been approved as the second- or third-line therapy for patients with unresectable or advanced/metastatic, dMMR/MSI-H positive colorectal cancers that have progressed on prior treatment (except a checkpoint inhibitor).
Role of Chemotherapy
Chemotherapy may be used for colon cancer in adjuvant setting (after surgical resection of tumor) or metastatic setting (palliative intent). Various chemotherapy regimens have been approved for colon cancer treatment.
Some drugs that are a part of treatment regimens for colon cancer include-
- 5 Fluorouracil
Best Colorectal Cancer Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of around 10 years of treating breast cancer patients. He has treated breast cancer patients with Chemotherapy, Targeted Therapy, Immunotherapy and Personalized Cancer Treatment. He is currently practicing at Manipal Hospital, Dwarka.
Diagnostic modalities available at our hospital include Colonoscopic biopsy, Whole Body PET CT, etc. Other treatment facilities for Colon Cancer available are Right Hemicolectomy, Left Hemicolectomy, Pancolectomy, Hartman’s Procedure, Colostomy, etc.
Call +91 9686813020 for appointment