The colonoscopy results were normal, so how come he suddenly got colon cancer?

Data show that colonoscopy screening for colorectal cancer, detecting early lesions and providing treatment can significantly reduce cancer mortality and save medical expenses, which is why colonoscopy screening has become an important part of middle-aged people's physical examinations. However, due to the imperfections of existing medical technology, some colorectal cancers will escape this screening, resulting in unacceptable consequences.

Written by Li Changqing (Doctor of Medicine, practicing physician in the United States)

A doctor colleague recently encountered a case of colorectal cancer. The patient had just undergone a colonoscopy in 2021, and it was completely normal at the time. Recently, due to symptoms, he repeated the examination and found that the sigmoid colon had been blocked by cancer and the colonoscope could not pass.

For patients who hope to detect colorectal cancer early through colonoscopy, this result is obviously difficult to accept. But in fact, similar cases are not uncommon. The academic community has a special term for this situation, called "Interval Colorectal Cancer" (I-CRC). Among all colorectal cancer cases, the proportion of interval colorectal cancer is not high, about 5%-8%, but because colorectal cancer is a high-incidence cancer, the total number is large.

The origin of the concept of intermittent colorectal cancer

To understand intermittent colorectal cancer, we must first have a general understanding of colonoscopy. The main purpose of colonoscopy is to screen for colorectal cancer. Evidence shows that for common colorectal cancer, detecting early lesions and providing treatment can improve the overall survival rate of the population, reduce cancer mortality, and save medical expenses.

Not all cancer screenings have such an effect. The high efficiency of colorectal cancer screening is related to its growth characteristics. Most colorectal cancers develop from colorectal adenomas. Adenomas are prominently manifested as polyps under endoscopy and can be removed almost non-invasively through endoscopy, thus preventing them from developing into colorectal cancer. Therefore, the main purpose of colonoscopy screening is to detect endoscopically resectable adenomatous polyps and remove them.

The so-called interval refers to the time between two colorectal cancer screenings, usually colonoscopy. Due to the high incidence of colorectal cancer and the benefits of colonoscopy screening, many countries recommend colonoscopy screening after a certain age. The current age requirement in the United States is over 45 years old. If there is a family history, individual adjustments are required. The time for the next examination is determined based on the results of the first colonoscopy.

If the first examination is completely normal, it is usually recommended to check again after 10 years; if there are 1-2 adenomatous polyps with a diameter of less than 1 cm, it is recommended to have a screening interval of 7-10 years; if there are 3-4 adenomas with a diameter of less than 1 cm, it is recommended to have a screening interval of 3-5 years; if there are 5-10 adenomas, or a single adenoma with a diameter greater than 1 cm and with villous adenoma characteristics or atypical hyperplasia, it is recommended to have a screening interval of 3 years; if there are more than 10 adenomas, it is recommended to have a screening interval of one year.

The intervals for such screening are based on the observation of the growth patterns of adenomas. An adenoma may develop from a single cell, first developing into an adenomatous polyp visible under colonoscopy, and then gradually developing into cancer. This process is of course impossible to observe directly, but it can be roughly estimated by analyzing the results of colonoscopy examinations of a large number of people.

The purpose of screening is to detect lesions before the patient develops symptoms. If symptoms appear and colonoscopy is performed, it is a diagnosis, not a screening. Therefore, determining the "residence time" of a lesion before causing clinical symptoms becomes the basis for screening intervals. The most cited study on this issue comes from Germany, where researchers analyzed the results of 1.88 million colonoscopies across Germany and estimated that the preclinical residence time of colon cancer is between 4.5 and 5.8 years. Taking an average of 5 years, the definition of intermittent colorectal cancer is colorectal cancer discovered within 60 months (a full five years) after the first normal colonoscopy.

However, some people have suggested shortening this period to 36 months (three full years), based on data from another study from National Taiwan University, which concluded that the time it takes for colorectal cancer to go from being asymptomatic to developing symptoms is 2.8 years.

The standard for this "stay time" has yet to be unified, but if colorectal cancer is discovered within three years after the first colonoscopy results showed normal results, there should be no controversy in diagnosing it as intermittent colorectal cancer.

If there are abnormal findings during the first colonoscopy, such as the above-mentioned number and size of polyps, and colorectal cancer is discovered before the next colonoscopy scheduled by the doctor, it is also considered intermittent colorectal cancer. Of course, the "interval" in this case cannot be based on the five-year or three-year standard, but should be based on the reexamination interval given by the doctor.

Four major causes of intermittent colon cancer

Intermittent colorectal cancer is somewhat difficult for both patients and doctors to accept. If colorectal cancer is diagnosed due to symptoms, it is an expected bad thing; if colorectal cancer is found through screening, it is an unexpected good thing; and intermittent colorectal cancer is an unexpected bad thing.

At present, the medical community believes that there are four reasons for intermittent colorectal cancer, the first of which is missed diagnosis. In theory, colonoscopy can observe every corner of the large intestine, but due to individual differences, some blind spots may be overlooked. The shape of the colon is like a series of bags connected together, and there is a wrinkle where the two bags meet. If a lesion is located on the side of the wrinkle that is not illuminated, it may be missed; the large intestine also has several fixed bends in the abdominal cavity, and some temporary bends will be produced during colonoscopy. Some patients will also have varying degrees of spasms, all of which may cause some lesions to be missed.

The second reason is inadequate colonoscopy. The most difficult technical aspect of colonoscopy, and the most important indicator of the operator's proficiency, is the proportion and speed of the colonoscope reaching the cecum. If a colonoscopy does not reach the cecum, it is considered incomplete. This is due to factors related to the patient and the operator. However, even the most skilled operator cannot guarantee that every patient can complete the procedure. This is because there are many variables in the operation of the colonoscopy. For example, a colonoscopy requires the use of laxatives to clean up the excrement in the intestine. If the intestine is not cleaned sufficiently, some lesions may be hidden in the fecal water in the intestine.

The third reason is that the lesion was not completely removed. This happens when an adenoma was found during the last colonoscopy and endoscopic resection was performed, but the lesion was not completely removed, resulting in cancer at the site of the last endoscopic surgery; or the cancerous lesion has invaded deeper tissues and can no longer be removed through endoscopy. The latter is relatively rare, because there is a routine pathological test follow-up after the endoscopic surgery, and only when the endoscopist and the pathologist make mistakes at the same time can a malignant result be caused.

The fourth reason is truly new cancer. Unlike the previous categories, this category is defined as cancer found more than 36 months after the previous examination.

The “human factor” dilemma

According to a survey in the Netherlands, among 147 cases of intermittent colorectal cancer, the proportions of missed diagnosis, inadequate examination, incomplete resection and new cancer were 57.8%, 19.8%, 8.8% and 13.6% respectively. The first three of them were related to operation, which means that nearly 90% of intermittent colorectal cancer was related to human factors.

Although there are some reports that intermittent colon cancer lesions may be different from other colon cancers, including being more common in the right colon and having different biological characteristics, these factors themselves will affect the difficulty of the operation. For example, the right colon is more difficult to observe and requires higher operation requirements. More importantly, these are factors that cannot be changed. You cannot ask patients to grow adenomas to the left colon as much as possible. However, human factors can be improved.

So where is the most critical human factor? It may still be the operator. Studies from the United States and Canada have found that if the first colonoscopy is performed by a non-gastroenterologist, the probability of intermittent colon cancer will increase. Especially in Canada, many colonoscopy screenings are performed by surgeons. Most colonoscopies in the United States are performed by gastroenterologists, but there are also many operators who are not gastroenterologists, including surgeons, internists, general practitioners, and even nurse practitioners (NP) and physician assistants (PA) can do colonoscopies.

Studies have suggested that if the colonoscopy is performed by a gastroenterologist, a person's risk of dying from colorectal cancer is reduced by 65%. The same indicators for general practitioners and surgeons are 57% and 45%, respectively. The risk of intermittent colorectal cancer may be one of the reasons for this gap. As for why there is such a gap, it may be related to the training process and continuing education of doctors in different specialties. Gastroenterologists receive longer and more systematic colonoscopy training, and they pay more attention to the progress related to colonoscopy after joining the work.

Should we restrict or cancel the colonoscopy performed by non-gastroenterologists? This is indeed a decision based on simple linear thinking, but it ignores an important fact, that is, colonoscopies performed by non-gastroenterologists are still beneficial to patients overall. As mentioned above, although the reduction in the risk of death from colon cancer by non-gastroenterologists is smaller than that by gastroenterologists, it is still a large reduction.

Another problem is that even in developed countries, doctors who are skilled in colonoscopy are still a scarce resource. Many places cannot hire gastroenterologists, so colonoscopy performed by non-gastroenterologists is a necessary supplement. In the US Veterans Affairs (VA) medical system, nurse practitioners and physician assistants are still one of the main personnel for colonoscopy examinations. Some studies have even shown that the quality of colonoscopy examinations by these two is better than that of gastroenterologists. Many researchers in the VA system have also been trying to promote their experience throughout the United States, but they are still resisted by the gastroenterology community.

In any case, although colorectal cancer is still the most common malignant tumor in developed countries, the incidence and mortality rates have declined for many years, thanks to colonoscopy screening, including these necessary supplements from non-gastroenterologists.

What should I do if I find intermittent colorectal cancer?

Although the occurrence of intermittent colorectal cancer makes patients sad and doctors embarrassed, current research has found that intermittent colorectal cancer is generally not at a high stage in cancer classification, most of them are in a treatable stage, and the survival period is not significantly different from that of general colorectal cancer.

The treatment of intermittent colorectal cancer is no different from that of other colorectal cancers, and both require collaboration among surgeons, internal medicine doctors, and oncologists. As patients and their families, you should not lose trust in regular medical care because of possible missed diagnosis, allow the tumor to grow, or seek help from quack doctors. Such irrational behavior will lead to more serious consequences.

Intermittent colorectal cancer is an example of how medical science and technology are not perfect, and perhaps also reflects the shortcomings of current public health and economic development. But like any imperfection, recognizing it and acknowledging it is the first step to improving it.

References

[1] Lee, YM, & Huh, KC (2017). Clinical and Biological Features of Interval Colorectal Cancer. Clinical Endoscopy, 50(3), 254–260. https://doi.org/10.5946/ce.2016.115

[2] Samadder, NJ, Curtin, K., Tuohy, TMF, Pappas, L., Boucher, K., Provenzale, D., Rowe, KG, Mineau, GP, Smith, K., Pimentel, R., Kirchhoff, AC, & Burt, RW (2014). Characteristics of missed or interval colorectal cancer and patient survival: a population-based study. Gastroenterology, 146(4), 950–960. https://doi.org/10.1053/j.gastro.2014.01.013

[3] Brenner, H., Altenhofen, L., Katalinic, A., Lansdorp-Vogelaar, I., & Hoffmeister, M. (2011). Sojourn time of preclinical colorectal cancer by sex and age: estimates from the German national screening colonoscopy database. American Journal of Epidemiology, 174(10), 1140–1146. https://doi.org/10.1093/aje/kwr188

[4] Chen, TH, Yen, MF, Lai, MS, Koong, SL, Wang, CY, Wong, JM, Prevost, TC, & Duffy, SW (1999). Evaluation of a selective screening for colorectal carcinoma: the Taiwan Multicenter Cancer Screening (TAMCAS) project. Cancer, 86(7), 1116–1128.

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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