Colorectal cancer (2)

Question 1

Pathogenesis/progression of colorectal cancer

Answer 1

Begins as a benign polyp (adenoma)
-this occurs in up to 53% of patients as we age
-this can be detected and removed with colonoscopy (which is why screening is important)

If it is not removed, polyps can grow and become cancerous - adenocarcinomas

It takes a while for a small polyp to become malignant (5-10 years), so after getting a colonoscopy they may tell you when you should come back to get another one based on what they find

Question 2

What are 2 hereditary conditions associated with colorectal cancer?

Answer 2

HNPCC (hereditary nonpolyposis colorectal cancer)
-not very common
-caused by a mutation that impairs DNA repair system
-tends to develop before age 50, so you should know if you have this in your family and get screened earlier
-not likely to have a lot of large polyps - they will just develop into cancer at a quicker rate
-if caught early, survival rate is good

FAP (familial adenomatous polyposis)
-patients have a lot of polyps
-develops earlier in life
-caused by mutations in the APC gene

Question 3

What is the biggest risk factor for colorectal cancer?

Answer 3

Age (50 and over… which is why this is when we start colonoscopy screenings)

Question 4

Colorectal cancer risk factors

Answer 4

Age over 50 (biggest risk factor)

Family history
-having a first degree relative increases risk x3

Health conditions
-Inflammatory bowel disease - ulcerative colitis or chron’s disease
-T2DM (poorer immune response = less damage repair, so higher risk and also worse prognosis with uncontrolled T2DM)

Race - african americans

Lifestyle
-diet high in fat and red meats (can be carcinogenic)
-diet low in fiber (fiber helps clear out colon, removing carcinogens)
-smoking (increased carcinogen exposure)
-limited physical activity (sedentary lifestyle = immune system doesn’t work as well to repair damages = more likely to have cancerous growths)

Question 5

Screening for colorectal cancer

Answer 5

For patients with “average risk”
-colonoscopy should be done starting at age 50 and repeated every 10 years (or sooner if they find something)

For patients with high risk due to family history
-colonoscopy should be done starting at age 40 or 10 years before earliest onset of family member (whichever is earliest) and repeated every 5 years

For patients with high risk due to IBD (UC or CD)
-colonoscopy should be done every 1-2 years

(patients with hereditary conditions HNPCC and FAP have different screening ages/frequencies too)

Question 6

Colorectal cancer symptoms/presentation

Answer 6

Symptoms are nonspecific and depend on which part of the colon the cancer originates from

If in ascending colon
-this is far from the rectum, so dark stools, may be hard to detect any change (patient’s may not notice anything because by the time it gets to the rectum the blood will be very dark)
-abdominal pain, weakness, weight loss, diarrhea

If in descending colon
-this is closer to the rectum, so the stool may be more red/detectable blood
-constipation/diarrhea, abdominal pain

If in rectum
-bright red blood
-rectal fullness, urgency, changes in bowel movements
-patients are more likely to present to the doctor

Question 7

Stages

Answer 7

Stage 1 has really good prognosis (56-100% 5 year survival rate)

Prognosis decreases with stage
Stage 4 = metastasis

Question 8

Which mutations should we look for with colorectal cancer? (2)

Answer 8

1. KRAS and NRAS mutation
   -all patients should be tested for this
   -if present, indicate a poorer prognosis, and KRAS mutations acquire resistance to EGFR therapy (so it is important to know if they have this, then we cannot use that therapy)
2. BRAF mutation
   -BRAF mutation indicates a worse prognosis

Question 9

Stage 1 colorectal cancer treatment

Answer 9

Surgery (remove primary tumor and regional lymph nodes)
+ surveillance

(chemotherapy may not even be required)

Question 10

Stage 2 colorectal cancer treatment

Answer 10

Surgery (remove primary tumor and regional lymph nodes)

Adjuvant therapy…
If “average risk” patient…
5-FU + leucovorin or capecitabine
-capecitabine is preferred by most patients because it is oral
(note leucovorin just enhances the efficacy of 5-fu)

If “high risk” patient (family history, genetic disorder, or IBD)…
can use the 5-FU + leucovorin or capecitabine, but preferred option is… FOLFOX (5-FU + leucovorin + oxaliplatin)
(if oxaliplatin can’t be tolerated, the other 2 options can be used)

Question 11

Stage 3 colorectal cancer treatment

Answer 11

Surgery (remove primary tumor and regional lymph nodes)

Adjuvant therapy…
FOLFOX (5-FU + leucovorin + oxaliplatin)
or
CapeOx (capecitabine + oxaliplatin)

either one can be used, based on patient preference

Question 12

Stage 4 colorectal cancer treatment

Answer 12

Here surgery is just palliative

Chemotherapy:
FOLFIRI (5-FU + leucovorin + irinotecan) - more common option
or FOLFOX (5-FU + leucovorin + oxaliplatin) or CapeOX (capecitabine + oxaliplatin)

Radiation can also be used for palliative care (helps with pain)

Question 13

Where does colorectal cancer mainly metastasis to?

Answer 13

The liver - this is why stage 4 is hard to treat, once it metastasis to the liver, it is pumped into the blood stream and will go everywhere

(bone is the next biggest metastasis site)