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Colorectal Cancer

Jenna Lombardo

Radiation Therapy Program, Nassau Community College

AHS 266: Radiation Therapy Lecture III

Carolyn Confusione

November 20, 2020

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Colorectal Cancer

Amounting to about half of all gastrointestinal malignancies, colorectal cancer is

considered to be the third most common cancer among men and women (Washington & Leaver,

2016, p. 705-706). According to the World Health Organization (2018), it can reach up to 1.80

million cases in a single year. In terms of mortality rates, colorectal cancer ranks second for

most common cause of cancer death, causing roughly 862,000 deaths across the globe and makes

up 9.6% of all cancer deaths (World Health Organization, 2018).

Colorectal cancer, or bowel cancer, refers to a cancer in either the colon or the rectum.

Although being notably similar, colon cancer and rectal cancer differ by the location of where

the tumor first develops, thereby changing their symptoms, diagnosis, and treatment methods.

Rectal cancer forms inside the last 5 to 10 inches of the large intestine, where the body stores

stool until a person has a bowel movement (Fight Colorectal Cancer). They account for

approximately 25% of all large bowel cancers (Lee, Y. C., 2013).

Epidemiology

As stated by Dr. Carolyn C. Compton (2020), countries with the highest incidence rates

and the lowest mortality rates also carry a high socioeconomic status that raises the risk by 30%.

These countries include Australia and New Zealand, Europe, and North America. High

incidence rates are due to higher prevalence of known risk factors, longer life expectancy, and

higher rates of detection and screening (Compton, 2020). Low mortality rates are due to

improved access to medical care, more effective treatment regimens, and screening examinations

that are catching cancers at an earlier stage which prevents 60% of cancer deaths (Compton,

2020). In contrast, countries such as Africa and South-Central Asia carry a low socioeconomic
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status and therefore have the lowest incidence rates and the highest mortality rates for the

opposite reasons (Compton, 2020).

Etiology

The incidence rate of colorectal cancer for men is approximately 25% higher than for

women (Compton, 2020). There is also higher incidence in older individuals, with those over the

age of 50 making up more than 90% of all colorectal cancer cases (Washington & Leaver, 2016,

p. 706). According to John Hopkins Medicine, the African American population takes the lead

for the highest incidence and mortality rates of all racial groups, being around 20% higher than

the caucasian population (Compton, 2020).

Diet increases the risk for colorectal cancer when correlating to the typical Western diet

that is high in calories, animal fat, processed meats and red meats (Mayo Clinic, 2020). As

claimed by the American Cancer Society, an unhealthy diet along with a lack of physical activity

increases obesity, and obesity raises both incidence and mortality rates for colorectal cancer.

Studies show that physically active people have a 25% lower risk of developing colorectal cancer

and are also less likely to die from the disease (American Cancer Society). Obesity is also

associated with type 2 diabetes, which is known for increasing the risk of colorectal cancer by

20% and leading to an unfavorable prognosis (ACS). Other unhealthy habits that are risk factors

include smoking tobacco and moderate to heavy alcohol consumption, with two to three

alcoholic drinks per day increasing the risk by 20% (ACS). Inflammatory Bowl Disease (IBD),

including Ulcerative Colitis and Crohn’s Disease, may develop dysplasia if left untreated and

increase the risk for colorectal cancer (ACS).

If a person had colorectal cancer in the past or if a person has received radiation treatment

in the past for any cancer to which the radiation beam was directed toward the abdomen, there is
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an increased risk for cancer development (MC, 2020). As reported by the American Cancer

Society, 1 in 3 people who develop colorectal cancer have other family members that have had it

in the past. Approximately 5% of people who develop the disease carry inherited gene changes

known to cause family cancer syndromes that typically involve adenomatous polyps (ACS).

Polyps are a significant risk factor since they are very common and most bowel cancers develop

from them (Cancer Research UK, 2018). The risk increases if the polyp is larger than 1 cm, if

more than 2 polyps are discovered, or if any of them show dysplasia (ACS).

Clinical Presentation

Since colorectal cancer typically begins as a small polyp, they usually produce very few

symptoms or non at all (ACS). As it grows, the initial symptoms shown are hematochezia or

rectal bleeding due to damaged rectal vessels, bowel changes such as diarrhea and constipation,

and narrowed or pencil-thin stool shapes from the tumor filling the rectal valve area (Washington

& Leaver, 2016, p. 709). Over time, the build up of blood loss from hematochezia can lead to

anemia and additionally cause weakness, fatigue, and pale skin (ACS). Other symptoms for

locally advanced disease include tenesmus, described as rectal spasms along with an urge to

empty the bowel but the feeling is not diminished by doing so (Washington & Leaver, 2016,

p.709). A later symptom that indicates possible extensive disease is pain in the buttock or

perineal area due to posterior tumor extension (Washington & Leaver, 2016, p. 709).

Routes of Spread

Colorectal cancer presents local spread via direct extension through tissue, and metastatic

spread via lymphatics and blood vessels (Washington & Leaver, 2016, p. 711). The tumor will

grow from the mucosal layer outward through some or all of the other layers of the bowel wall.

Once it reaches the next layer known as the submucosa, it is now able to grow into the lymph
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vessels or blood vessels and travel to nearby lymph nodes or other distant parts of the body

(Washington & Leaver, 2016, p. 711). If it invades all layers of the bowel wall, it can directly

reach the peritoneal surface or adjacent structures of the pelvis depending on where the tumor is

located inside the rectum (Washington & Leaver, 2016, p. 707).

The upper and middle portion of the rectum is covered by the peritoneum on the anterior

surface (Washington & Leaver, 2016, p. 707). Once there is invasion through the bowel wall for

tumors in these areas, they have the ability to extend into the peritoneum and cause peritoneal

seeding. This is when tumor cells are shedding into the abdominal cavity and causing additional

cancer growth on other surfaces (Washington & Leaver, 2016, p.711). The lower portion of the

rectum lacks peritoneum and is closer to adjacent structures of the pelvis, possibly leading to

invasion of the sacrum, bladder, prostate, and vagina (Washington & Leaver, 2016, p. 707).

Colorectal cancer commonly spreads via lymphatics first, with roughly 50% of all

patients presenting positive nodes for tumor at diagnosis (Washington & Leaver, 2016, p.711).

The initial nodes reached via direct extension are the perirectal lymph nodes, while other

surrounding nodes may be reached via lymphatic vessels that drain the rectum (Washington &

Leaver, 2016, p.711). As reported by Washington & Leaver, drainage for the upper and partly

middle portion of the rectum follows the superior rectal lymphatic vessels into the nodes along

the inferior mesenteric artery. For the middle and inferior portion, the middle rectal vessels and

the inferior rectal vessels both drain into the internal iliac nodes.

Distant metastasis is possible via hematogenous spread, making the liver the most

common site for malignant colorectal cells to travel to (Washington & Leaver, 2016, p. 711).

Liver metastasis will eventually occur in up to 70% of patients diagnosed with colorectal cancer,

which is mainly due to the liver receiving most of its blood supply from the portal vein that is
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directly connected to the intestines (Memorial Sloan Kettering Cancer Center). Symptoms of

liver metastasis include leg edema, abdominal ascites, nausea, fatigue, weight loss, fever, itchy

skin, and jaundice (MSKCC). The second most common site for distant metastasis is the lung,

due to tumor embolus or broken off tumor fragments that travel through the blood stream via the

middle inferior rectal veins into the inferior vena cava (Washington & Leaver, 2016, p. 711).

Symptoms for lung metastasis include chronic cough, shortness of breath, dyspnea or difficulty

breathing, hemoptysis or coughing up blood, pain, and fatigue (Markman, 2020).

Diagnostic Work-Up

If a person is experiencing symptoms of colorectal cancer or if screening examination

results came back abnormal, there will be additional testing done to collect more information and

determine if cancer is present (Fight Colorectal Cancer). Ultimately, the first procedure that

should be done is a colonoscopy, since it allows the doctor to thoroughly examine the entire

colon and gives the ability to remove any polyps or obtain any biopsies needed for an official

cancer diagnosis (Washington & Leaver, 2016, p. 709). Once a cancer diagnosis is histologically

confirmed, the patient will go through a diagnostic work-up to determine the extent or amount of

spread of the disease, commonly known as the stage (MC, 2020). This is crucial to designing the

best and most effective treatment plan tailored specifically to the patient and their cancer (John

Hopkins Medicine).

The diagnostic work-up typically includes the patient’s medical history, physical

examination, endoscopic procedures, radiologic imaging, and laboratory studies. For medical

history of a patient, the doctor may learn possible risk factors such as family history, symptoms

experienced by the patient, and when those symptoms began (ACS). A physical examination will

identify any possible swelling, tenderness, and unusual growths or masses in the pelvic and
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abdominal areas, and assess potential sites of distant metastasis (ACS). It should also include a

digital rectal examination, where the doctor inserts a gloved finger into the rectum to feel for any

abnormal areas, focusing on the tumor’s size, mobility, location from the anal verge, rectal wall

involvement, and possible detection of enlarged perirectal nodes (Washington & Leaver, 2016, p.

709).

Endoscopic procedures, typically involving a colonoscopy and a proctosigmoidoscopy,

can be useful in evaluating the tumor size, location, circumferential extent, and distance from the

anal verge (Washington & Leaver, 2016, p. 709-710). Proctosigmoidoscopy may also be used to

discover if the tumor is exophytic or ulcerative (Washington & Leaver, 2016, p. 709).

Radiologic imaging can be used for both local and distant staging. Local staging is done

with MRI or ultrasound because both imaging modalities demonstrate higher quality images of

organs and soft tissue than other scanning techniques (MSKCC). For this reason, we use these

two imaging techniques to evaluate the tumor’s depth of penetration through the bowel wall, and

if it has extended into other pelvic organs, lymph nodes, or other nearby structures (American

Society of Colon & Rectal Surgeons). We may also use MRI and ultrasound for the abdomen to

determine or verify suspected metastasis to organs such as the liver (National Cancer Institute).

According to the American Society of Colon & Rectal Surgeons, distant staging is typically done

with CT and PET scans because CT scans precisely detect most cancer cells that have spread

outside the rectum, while PET scans determine location by highlighting any areas of uptake

throughout the body. A CT scan of the chest is used to detect metastasis in organs such as the

lung, while a CT scan of the abdomen is used for the liver (National Cancer Society).

Laboratory studies include a complete blood count, blood chemistry profile, and

carcinoembryonic antigen testing (CR UK). A complete blood count measures the different types
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of cells in the blood and is used to determine if red blood cell counts are low because this may

indicate chronic rectal bleeding (CR UK). It can also be used to check if the white blood cell

count is high because this shows the presence of an infection that may be from tumor growth

through the wall of the rectum (ACS). A blood chemistry profile shows measurements of the

different chemicals in the blood that can be used to measure the functioning of organs, the most

significant organ here being the liver. Elevated liver enzymes reveal possible liver metastasis and

must be followed up with a CT or sonogram (CR UK). The levels of carcinoembryonic antigen

in the blood are stated to be an indicator of disease when elevated above normal. Specific types

of protein molecules, also called tumor markers, are produced by certain cancers that may

suggest this same cancer is present in the body. It is another testing method used for distant

staging because the higher the level of this antigen, the more disease may be present

(Washington & Leaver, 2016, p. 710). Therefore, this testing method is particularly useful in

monitoring patient response to treatment, showing an early warning of possible recurrence, and

identifying if a cancer is advanced or widespread (MC, 2020).

Pathology and Staging

After the diagnostic work-up is complete, there is enough information about the cancer to

determine how large the tumor is and whether it has spread, but these are not the only factors

used when determining the cancer’s stage (CR UK). Pathology testing to discover the cell type

and cell grade of the malignant tumor must be involved during the staging process for greater

accuracy, and is especially important when looking to identify the best treatment regimen (ACS).

Since bowel cancer tends to originate from the glandular epithelial cells that line the inner

mucosal layer, the most common cell type for colorectal cancer is Adenocarcinoma which makes

up 90% to 95% of all tumors in the large bowel (Washington & Leaver, 2016, p.710). According
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to the American Cancer Society, approximately 80% of adenocarcinomas in the large bowel are

considered to be of a lower grade or moderately differentiated, and the remaining 20% are of a

higher grade or poorly differentiated. The second most common malignant cell type is Mucinous

Adenocarcinoma, comprising about 5% to 10% of all colorectal cancers and has a better

prognosis than classic Adenocarcinoma (CR UK). Other less common histologic types include

Signet-Ring Cell Carcinoma and Squamous Cell Carcinoma (Washington & Leaver, 2016,

p.710).

The most common staging system used for colorectal cancer is the TNM system, and

includes the two most important prognostic factors known as the number of positive lymph

nodes involved and the depth of penetration through the bowel wall (Washington & Leaver,

2016, p. 710). The five year survival rates for localized rectal cancer in stages 0 and 1 are around

89%, then decreases to about 71% for stage 2 and 3 lesions, and eventually drops all the way

down to 15% for stage 4 lesions (ACS). Figure 1 shows the staging classification for colorectal

cancer according to the American Joint Committee on Cancer…

Figure 1

American Joint Committee on Cancer staging classification for colorectal cancer

Treatment

There are multiple different approaches for the treatment of rectal cancer, including

surgery, chemotherapy, and radiation therapy. The primary treatment is surgery, but this
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approach may vary due to the patient’s overall health, stage, location of the tumor inside the

rectum or distance from the anal sphincter muscle, and existence of high-risk features such as

poor differentiation, positive margins, perineurial invasion, and lymphovascular invasion (NCI).

As stated by the American Cancer Society for stage 1 cancers, the typical treatment

regimen is surgery with or without chemoradiation. Possible surgical operations for low stage

rectal cancers include local transanal resection for removal of the tumor plus a small amount of

healthy tissue surrounding it (ACS). Cancers in stage 2 and stage 3 are treated with both surgery

and chemoradiation, and these surgical procedures tend to be more invasive operations but may

still be used for stage 1 lesions if needed (ACS). These surgeries include low anterior resection

for removal of all or part of the rectum, and abdominoperineal resection for removal of the entire

rectum and anus (CR UK). This surgical procedure is typically done for patients with tumors in

the inferior third portion of the rectum (CR UK). The administration of chemotherapy and

radiation treatments may be done together or separately from each other, either in the pre-

operative or post-operative setting (ACS). Cancers that are stage 4 are usually treated by surgery

with or without chemotherapy or radiation therapy (ACS). The typical surgical procedure done

for this stage is a pelvic exenteration for the removal of the rectum plus any nearby organs that

the cancer has spread to such as the bladder, prostate, or uterus (ACS). If the cancer is unable to

be resected, radiation and chemotherapy are typically combined but may also be used alone for a

palliative treatment regimen in most cases (ACS).

When receiving radiation treatment for rectal cancer, patients should be placed head first

on the treatment table in the prone position with full bladder distention (Washington & Leaver,

2016, p. 713). This position pushes the organ at risk out of the treatment field commonly known

to be the small bowel, which has a tolerance dose of only 45 Gray (Washington & Leaver, 2016,
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p.713). Using a 3-field technique involving one posteroanterior field and 2 opposed lateral fields

also helps with the sparing of surrounding structures and organs (Washington & Leaver, 2016, p.

713). In a case where surrounding structures or organs such as the prostate and vagina must be

irradiated, a 4-field technique is used instead which incorporates an anteroposterior,

posteroanterior, and 2 opposed lateral fields to provide radiation to those anterior structures

(Washington & Leaver, 2016, p. 713). The dose for large volume fields including the tumor and

regional nodes is 45 Gray, and the cone-down treatment field including only the primary tumor

bed receives 50 to 55 Gray over 6 to 6.5 weeks (Washington & Leaver, 2016, p. 713). More

recent radiotherapy techniques such as IMRT or VMAT offer a major advantage to the patient.

These techniques provide a higher conformal dose to the tumor and limit the dose to surrounding

critical structures for a reduction of unwanted side effects caused by radiation (Washington &

Leaver, 2016, p. 713). Endocavitary radiotherapy may also be used for smaller exophytic tumors

in the inferior to middle portion of the rectum that are confined to the bowel wall, with well to

moderate differentiation (Washington & Leaver, 2016, p. 713). The total dose received is 120

Gray, split into four fractions of 30 Gray each given every 2 weeks, for an intention to cure

without surgery and preserve the anal sphincter muscle (Washington & Leaver, 2016, p. 711).

After analyzing the multiple treatment modalities used for rectal cancer, my treatment of

choice for locally advanced cancer is pre-operative chemoradiation and surgery. Pre-operative

chemoradiation is used to shrink the tumor before surgery, making for a much easier and far less

invasive surgery (ACS). This will decrease the chances of the tumor seeding or spilling out

during resection (ACS). This also allows preservation of the anal sphincter muscle because low

anterior resection will replace abdominoperineal resection (ACS). If this muscle is preserved,

bowel control is preserved along with it, so waste can leave the body normally and save a person
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from major emotional distress (ACS). Pre-operative chemoradiation has several advantages over

post-operative treatment, starting with the lessening of radiation dose to the small bowel. Since

post-operative chemoradiation involves a more invasive surgical method, the rectum and

peritoneum would have been removed during surgery, causing the small bowel to move more

inferiorly and possibly into the treatment field (Washington & Leaver, 2016, p. 711). The side

effects are also significantly reduced in pre-operative chemoradiation, showing acute effects in

27% of patients and long term effects in 14% of patients (NCI). Post-operative treatment side

effects are much higher, showing acute effects in 40% of patients and long term effects in 24%

of patients (NCI). When chemotherapy is combined with radiotherapy, certain drugs are

commonly added that may act as radiosensitizers to the cells, ultimately helping the radiation

damage the cancer cells (NCI).

It is safe to say that the colon and rectum are extremely significant parts of the body,

which is why it is crucial to preserve as much organ function as possible when choosing a

treatment regimen for these tumors. This is not only physically important to the patient, but

mentally and emotionally as well. If there is a way to avoid an extremely invasive surgery or

unwanted side effects that will reduce the patient’s quality of life, they should be taken into

consideration.

References

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