Introduction

Andy's case history, which was described in the previous article in this series (see first link below), attempted to illustrate only one of many issues involved with screening for cancer in general: one should have realistic expectations on the meaning of test results, and then decide on the next course of action. Before embarking on any screening program, everyone at average risk for the disease in question should have information on the anticipated benefits and risks. Andy's case will be used again to illustrate how one can best formulate questions to evaluate the risks and to take an informed decision.

The case

Now he's better prepared, Andy has written a checklist of things he thinks he should know before deciding whether or not to have further testing and additional, as yet unknown, examinations. He knows that the risks for his actually having colorectal cancer are no higher than 1 in 20, even if he tests positive for fecal occult blood (FOB); however, that doesn't help him much regarding the next decision he should take. He wants to acquire some more crucial information.

Andy's checklist

What are the anticipated benefits if I comply with a screening program? Are there inconveniences associated with it and how great, if any, are the risks? What are the components of this program and how long should I continue with it?
In other words, Andy is now prepared to look ahead to find out if the next steps are worth taking.

Which benefits can I anticipate if I decide in favor of a screening program?

Another way to phrase this question could be: What are my overall chances of avoiding death from colorectal cancer if I comply with a screening program? To determine this before entering a screening program, I just need to ask my physician what are the risks of dying from colorectal cancer if I don't participate in the program and what are the risks of participating in the program.

Three very large studies involving more than 335,000 subjects between 45 and 80 years old were enrolled in the 1970s and have now completed a follow-up of 13 years or more. These studies were carried out in the USA, the UK and Denmark.^{1 2 3 4} All of them have shown consistency in the reduction of mortality due to colorectal cancer in those subjects who underwent screening, compared with those who didn't undergo the screening tests proposed. From these studies one can calculate that screening reduces lifetime colorectal cancer mortality from 29 to 19 deaths in 10,000 subjects who enrolled.⁴ In absolute terms, lifetime mortality from colorectal cancer decreases by one (from 3 to 2) in 1,000 for those who undergo screening. In relative terms, it decreases by one third.

What does this mean for me if I participate in this program? What needs to be done and how long should I do it to get the full benefit?

The FOB test

The benefits of mortality reduction were obtained when subjects agreed to screening using the FOB test. Basically, this test checks for the presence of blood in the stools and requires, as you can imagine, the collection of small stool samples. This can be done on easy-to-use slides. Preferably performed on 2 or more separate samples, the collection should not be done for cancer screening if you are taking certain medications (aspirin or other non steroidal anti-inflammatory agents), if you have known inflammatory bowel disease (ulcerative colitis or Crohn's disease), or if you suffer from hemorrhoids. In addition, meat and poultry should also be avoided, from at least 2 days before starting the sampling. So you see that the test is fairly simple. There is no inconvenience associated with this test, other than that linked to stool collection, observing dietary precautions and correctly implementing the instructions for labeling and shipping the slides to the lab for analysis.

The FOB test was done every two years on each participant in the studies mentioned above, except in the American study, which recommended the test be done every year. Let's assume that the screening program proposed to you would recommend the FOB test every 2 years. In this case, there would be seven FOB tests over a period of 14 years, and during this period, 5 people out of 100 will show a positive test. However, if the screening were done as in the American study (every year), more people would show up with a positive result - approximately one in four. There are almost no risks associated with the performance of the FOB test, other than the emotional burden associated with a positive test that's unrelated to cancer or any serious disease of the gastro-intestinal tract.

Colonoscopy

You know from Andy's previous experience that the FOB test may be positive even when no cancer is present. However, a positive test is a trigger to proceed with further investigations. The purpose of these is to diagnose the origin of bleeding, to check for the presence of lesions and remove them. This is best achieved with colonoscopy, which is superior to radiography in detecting small, early lesions.

Colonoscopy is an invasive procedure, performed with a colonoscope, an optical instrument consisting of a flexible tube so arranged that a person looking through the eyepiece at one end can see objects reflected at the other end. The other end of the tube is introduced into the inside (lumen) of the intestine through the anus; the tube is long enough to allow exploration of the full length the large bowel. You can imagine that a clear view within the lumen of the bowel requires it to be as empty as possible. To achieve this, you'll have to drink a large amount of a special salt solution the night before the procedure, or to follow a special diet for the 3 days preceding it. This can give you some abdominal cramps in addition to the slight inconvenience of adhering to the diet.

The procedure is carried out after you've been given a fairly strong sedative by IV injection. The physician doing the examination has been trained in the use of the colonoscope, which is also able to remove small pieces of tissue that look abnormal. This can serve as treatment if the lesion is at an early stage and hasn't spread. The removed tissue is sent for microscopic examination by a pathologist, the result of which will determine the further course of action (no need for treatment, surgery, or something else). The whole procedure takes around 60 to 90 minutes. During this time, you will have to lie down on your side without moving except when the physician asks you to do so.

The procedure does not require hospitalization. The strong sedation may affect your driving ability for a few hours. In very rare cases, colonoscopy may be associated with a serious adverse event, such as perforation of the bowel wall, hemorrhage, and even death. The risk of death associated with colonoscopy is very small; it has been estimated to be 1 in 20,000 procedures. This estimate comes from studies of colonoscopy in patients presenting with symptoms and sometimes serious underlying disease, so that the risks in a normal healthy population are likely to be lower, but how much lower is difficult to guess.

Once you accept the principle of screening with FOB, a positive result will almost inevitably lead to colonoscopy. We already know that the risk of having a positive FOB test over a 14-year period varies from 1 in 20 to 1 in 4, depending on how often you undergo testing. Therefore, the risk of having at least one colonoscopy is also between 1 in 20 and 1 in 4. Of course, if colonoscopy reveals the presence of abnormal tissue, other treatment options will be proposed, such as surgery or medical treatments, including follow-up colonoscopies. You should see these additional investigations as potentially beneficial, since they are part of a treatment you would have received at a later, more advanced and less curable stage of colorectal cancer.

Summary and conclusions

Starting at 50 years of age, the lifetime risk of dying from colorectal cancer is estimated to be 3 in 1,000. Participation in a screening program can reduce your chances of dying from that disease from 3 to 2 in a 1,000. The net anticipated benefit is therefore 1 in 1,000. However, you can also say that if you were one of the 3 in the 1,000 persons who started screening when they were 50 years old, your risk would decrease from 3 in 3 (100%) to 2 in 3 (66.6%), which is a 33% relative risk reduction or reduction by one third.

This reduction can be achieved when you perform the FOB test at least every 2 years until you are 75 years old. Altogether, over 25 years of your life, starting at 50, you will do a maximum of 12 FOB tests for which there are no risks and only a few inconvenient days for collecting the samples. If all your FOB tests are negative, your risk of dying from colorectal cancer is still 15 in 10,000, since unfortunately, the test fails in half of the CR cancer. If the FOB tests positive, colonoscopy or another equivalent diagnostic test will be proposed. Your lifetime risk for an FOB test being positive is around 1 in 20 and, likewise, your lifetime risk of having a colonoscopy is also 1 in 20. Colonoscopy is a very safe procedure with lifetime risk of death estimated at around one in 20,000.
This represents the necessary information for you to take an informed decision on whether or not you sign up for a screening program against colorectal cancer. You know the absolute risk of dying from cancer, the absolute risk reduction that the program brings (1 in 1,000 over 20 years), and what it entails to implement it.