Colo-Rectal Cancer

Colorectal cancer strikes 140,000 people annually making it the second most common cancer in the United States but thanks to early detection it is curable in most cases.  The predisposing factors for colon cancer are polyps, ulcerative colitis, Crohn’s disease, previous radiation therapy that involved the pelvis such as uterine and cervical cancer or seminoma of the testicle, and a history of colon cancer in family members. 

In most cases the exact cause of colorectal cancer is unknown. We do know that in populations that consume a high-fiber low-fat diet as do many cultures in Africa the incidence of colon cancer is extremely low.   In Western society however, industrialization and mass production of foods since the late 1800s has reduced the amount of fiber in the diet.  Along with the reduction of fiber, the bulk of stool has been reduced, the bacterial flora has changed, and transit through the colon is slower. 

By tracking markers that have been eaten with test meals researchers have found that food reaches the stomach in seconds, moves out of the stomach in three hours, and  travels through the small bowel for another three hours to reach the colon.  The first traces of these markers can be seen in stool in 24 hours and the last of them seven days later.  This long travel window allows any carcinogens that have been produced by bacterial action on chemicals in ingested foods more time to impact the lining of the colon.  The small bowel, however, is protected from the carcinogen impact because it is devoid of bacteria and digestive transit there is quite fast.

There are two distinct hereditary forms of colorectal cancer.  One is associated with polyps: familial adenomatous polyposis (FAP), and the other form presents without polyps: hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome type I and type II).  Colorectal cancer has special characteristics in people with these hereditary syndromes and when a familial form of colorectal cancer is suspected, genetic testing can be done on the patient and first degree relatives.

When colorectal cancer develops from a simple polyp (without the risk factors noted above) the progression is actually quite slow, taking many years to produce symptoms such as blockage or bleeding.   That is why surveillance colonoscopies are extremely important to detect polyps before they become cancerous.  The first colonoscopy is generally recommended at age 50, but if predisposing factors are present, it is best to start earlier, usually by age 40.  Although the instinctive reaction is to have surgery as soon as the diagnosis is made, the very fact that colorectal cancer is a slow-growing process allows us time to refine the diagnosis and best prepare for surgery rather than rushing to the operating room.

Cure of colorectal cancer is currently achieved in 90% of patients with early stages and in 50% of those with advanced disease.  Surgery remains the main therapy for the cure of colorectal cancer.  In some cases of rectal cancer, chemotherapy and radiation therapy are given before surgery (neoadjuvant therapy) to make the operation more effective and to avoid the complete removal of the rectum with the anus.  In colon cancer, chemotherapy may be necessary following surgery (adjuvant therapy) if the staging of the cancer after pathological analysis suggests potential spread of the tumor.  Less than 5% of patients with rectal or colorectal cancer will need a permanent colostomy which is the exteriorization of the colon through the abdominal wall to allow for feces collection in a plastic pouch. 

Staging the cancer


The decision for chemotherapy and radiation is based on staging of the cancer by the pathologist.  The pathologist will analyze the surgical specimen for the depth of the tumor invasion across the wall of the intestine, the presence of tumor cells in lymph nodes, and the presence of tumor cells at distant organs such as the liver or lung which is also known as metastasis.  The pathologist will also report other factors that define the behavior of the tumor such as the presence of tumor cells within blood and lymphatic vessels, genetic markers or “oncogenes” and the degree of differentiation of the cells (well differentiated cells are close to normal while poorly differentiated cells are abnormal).

Recent technological advancements now make rectal cancer staging possible before surgery by using transrectal ultrasound or a special form of MRI (magnetic resonance imaging).  Similar to the pathological staging system, the depth of tumor penetration and the presence of enlarged lymph nodes determine the staging of the tumor.  If the tumor is at a favorable stage the surgery can be limited to a local excision through the anus (if reachable) or through the abdomen.  If the tumor is deemed to be at an unfavorable stage, neoadjuvant therapy is given before surgery.

The most common pathological staging system is the TNM (tumors/nodes/metastases) system in which patients are assigned into a stage according to the American Joint Committee on Cancer (AJCC) as noted below.

T - The degree of invasion of the intestinal wall
Tis- cancer in situ (tumor present, but no invasion)
T1 - invasion through submucosa into lamina propria (basement membrane invaded)
T2 - invasion into the muscularis propria (i.e. proper muscle of the bowel wall)
T3 - invasion through the subserosa
T4 - invasion of surrounding structures (e.g. bladder) or with tumor cells on the free external surface of the bowel
N - The degree of lymphatic node involvement
N0 - no lymph nodes involved
N1 - one to three nodes involved
N2 - four or more nodes involved
M - The degree of metastasis, i.e., deposits of tumor at distant organs such as the liver
M0 - no metastasis
M1 - metastasis present

 

Stage


T


N


M


5 year survival*


Adjuvant Chemotherapy Recommended


O

 

Tis

 

N0

 

M0

 

100%

 

No

 

I

 

T1 or 2

 

N0

 

M0

 

93%

 

No

 

II A

 

T3

 

N0

 

M0

 

85%

 

Usually not

 

II B

 

T4

 

N0

 

M0

 

72%

 

Usually not

 

III A

 

T3

 

N1

 

M0

 

83%

 

Yes

 

III B

 

T4

 

N1

 

M0

 

64%

 

Yes

 

III C

 

Any T

 

N2

 

M0

 

44%

 

Yes

 

IV

 

Any T

 

Any N

 

M1

 

8%

 

Yes

 

* This figures represent the percentage of survivors at 5 years following surgery and is based on a study of the National Cancer Institute's SEER database, looking at nearly 120,000 people diagnosed with colon cancer between 1991 and 2000.  Newer forms of therapy have significantly improved these figures but there is not enough data to build survival tables yet

FOLFOX is the most common chemotherapy regimen for treatment of colorectal cancer. It consists of 3 drugs:
FOL– Folinic acid (leucovorin) F – Fluorouracil (5-FU)  OX – Oxaliplatin (Eloxatin)

FOLFOX4: Adjuvant treatment in patients with stage III colon cancer is recommended for 12 cycles, 2 days each cycle, every 2 weeks.

Side-effects of oxaliplatin treatment can potentially include:

Neuropathy, both an acute, reversible sensitivity to cold and numbness in the hands and feet and a chronic, possibly irreversible foot/leg, hand/arm numbness, often with deficits in proprioception (the sense of the relative position of neighboring parts of the body) fatigue, nausea, vomiting, and/or diarrheal, ototoxicity (hearing loss)
In addition, some patients may experience an allergic reaction to platinum-containing drugs.

Bevacizumab (Avastin) is new class of drugs used to treat metastatic colorectal cancer, stage IV, called anti-angiogenic agents. These drugs slow down the process of angiogenesis or growth of blood vessels. Tumors derive oxygen and nutrients for their own growth through the growth of these new blood vessels.  It is used in combination with some of the chemotherapeutic agents mentioned above.  In addition to the side effects already mentioned for FOLFOX, Avastin can produce:
Bleeding or bruising easily, loss of hair, mouth sores, rash on the hands and feet, tingling or numbness in fingers or toes

 

• • •