Cancer screening for a disagreement? Only when these conditions are met can cancer screening be worthwhile

After Fanpu published "Some cancer screenings are useless or even harmful" and "Tumor marker screenings popular in physical examinations, none of which have been approved, have become popular", many readers are concerned about which tumor screenings are beneficial and want to learn more about the basis. This article attempts to answer this question.

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

The cancer screening currently recommended by many medical institutions and physical examination companies is unnecessary, and many screening methods lack sufficient scientific basis. However, not all cancer screening is unnecessary. Early screening is still one of the important means of cancer prevention and treatment.

So, what are the cancer screenings that the medical science community believes are worth recommending? What is the basis for recommending these screenings? The following analyzes the major conditions that these cancers that are worth screening must meet. The screening mentioned here refers to cancer screening recommended for healthy people, including healthy people of a certain age and gender; screening for certain special high-risk groups, such as those exposed to radiation and infection sources, or those with a specific genetic family history, is not within the scope of this article.

Condition 1: High morbidity and mortality

The cancers recommended for screening for ordinary people should be common cancers with a high incidence rate. A high incidence rate means that screening can more likely detect "hidden" cancer patients, which can benefit more people. If the cancer has a very low incidence rate, screening can only detect a small number of patients, which is disproportionate to the cost and risk of large-scale screening. Medical resources are limited, and it is impossible to take into account all cancers. It is a realistic approach to give priority to screening cancers with a high incidence rate and a large impact on the population and society.

Therefore, the cancer screenings recommended for healthy people are almost all common and highly prevalent cancers. Taking the US Preventive Services Task Force (USPSTF) as an example, the cancer screenings recommended to the public are all common and high-mortality cancers (note: this is not the case fatality rate, which is the ratio of the number of people who die from a certain disease in a specific area to the total number of people with the disease, and the mortality rate is the ratio of the number of people who die from a certain disease in a specific area to the total number of people in that area), including breast cancer, cervical cancer, colorectal cancer, prostate cancer, and lung cancer. The specific screening recommendations are as follows:

Lung cancer: For people aged 50-80 years with a smoking history of more than 20 years (the number of packs smoked per day multiplied by the number of years of smoking is greater than 20), as well as those who have smoked this amount and have quit smoking for less than 15 years, a low-dose chest CT scan once a year is recommended.

Colorectal cancer: Age 45-75 years, full colonoscopy every 10 years, or high-sensitivity occult blood test once a year, or sigmoidoscopy every 5 years. If polyps are found during colonoscopy, the screening interval should be shortened according to the number and pathological type of polyps.

Breast cancer: Mammography screening every two years for women aged 50-74.

Cervical cancer: For those aged 21-29, a cervical smear test every three years; for those aged 30-65, a cervical smear test every three years, or high-risk human papillomavirus screening every five years (can be done alone or in combination with a cervical smear test every five years).

Prostate cancer: For men aged 55-69, whether to conduct regular prostate cancer screening should be individualized, and individuals need to understand the possible benefits and harms of screening. For men over 70 years old, routine screening is not recommended.

If you compare the cancers with the highest incidence and mortality rates with the cancers recommended for screening, you will find that some cancers with high incidence and mortality rates are not within the recommended screening range, such as pancreatic cancer and liver cancer. In other words, high incidence and mortality rates are not sufficient conditions for screening recommendations, and other conditions must be combined.

Condition 2: Cancer residence time

The art of war requires knowing both the enemy and yourself, and the same is true for cancer, the enemy of human health. Whether it is screening, diagnosis or treatment, it is limited by our understanding of a certain cancer, including its etiology, occurrence mechanism, growth pattern, morphology at different stages, and the impact of different stages on human life expectancy and quality of life.

When it comes to cancer screening, a key issue is knowing the sojourn time of cancer. A cancer may exist for many years or even decades before it causes symptoms and threatens health. The sojourn time refers to the duration from when the cancer can be detected by current technology (in terms of morphology) to when symptoms appear. This time cannot be too short or too long. If the sojourn time is too short, it will be difficult to detect early lesions, or intensive and repeated screening will be required; if the sojourn time is too long, the cancer will not cause symptoms in many people's lifetime, so screening will only lead to overdiagnosis and treatment. The most suitable sojourn time for screening is generally a few years.

It is not easy to determine the average length of stay of a cancer, which often requires years of collaborative research and observation in multiple fields of basic, clinical and public health. Even for the same tumor, some subtle differences may lead to different lengths of stay, so only an average value can be taken. For example, it is generally believed that the length of stay of breast cancer is 1-2 years, colorectal cancer is 2-4 years, prostate cancer is 3-7 years, and lung cancer reports vary, which may be between a few months and several years.

For many cancers, it is currently impossible to determine the dwell time and give appropriate screening recommendations, such as liver cancer, pancreatic cancer, ovarian cancer, etc. Most of these cancers cannot be diagnosed until symptoms appear. The difficulty in screening these cancers also involves another key issue about screening, which is the identification and elimination of early lesions.

Condition 3: Early lesions can be detected and eliminated

The purpose of cancer screening is to detect early lesions and eliminate them, thereby preventing the occurrence of advanced cancer. Early lesions can refer to relatively limited cancers, such as breast cancer that has not metastasized, and lesions that have a higher risk of becoming cancerous but have not yet become cancerous, such as colorectal adenomas.

From this perspective, to achieve the purpose of early screening, three conditions are required: the existence of early lesions, the early lesions can be detected, and the early lesions can be easily removed.

Theoretically, any cancer has early lesions, including early cancer and precancerous lesions. However, due to the limited level of medical development, for most cancers, we currently do not know what their early lesions look like. Even if there are, it is difficult for us to find them due to the limited level of technology. Most of the cancers recommended for screening are "lucky ones" that are the result of the combination of knowledge and technology.

Taking colorectal cancer screening as an example, whether it is a colonoscopy after fecal occult blood or DNA testing, or a direct colonoscopy, the main purpose is to detect colorectal adenomas. Statistics show that 70%-90% of colorectal cancers develop from adenomas, and colorectal adenomas are clear precancerous lesions of colorectal cancer. Colorectal adenomas can be observed intuitively under colonoscopy, and resection is also very convenient, so colonoscopy has become an ideal means of colorectal cancer screening.

Although the precancerous lesions of breast cancer are not as obvious as those of colorectal cancer, both ultrasound and mammography are non-invasive and convenient, and it is not difficult for surgeons to remove local lesions.

As for liver cancer, pancreatic cancer, and ovarian cancer, not only do we know very little about their early lesions, but if suspicious lesions are found, further diagnosis and removal are difficult. Liver puncture requires ultrasound or CT guidance, and pancreatic puncture requires ultrasound endoscopy guidance. The technology is difficult and has a high false negative and false positive rate. Surgical removal of lesions requires a more invasive operation, which is more demanding for the surgeon and has the risk of postoperative complications.

So, with the knowledge and elimination technology for precancerous lesions or early cancers, is it worth recommending screening? Not enough, we also need to touch on the last issue discussed in this article: evidence-based medicine.

Condition 4: Evidence-based medicine

The medical science community adopts the principle of presumption of guilt for a specific diagnostic and treatment method, that is, if there is not enough evidence to prove that the method is safe and beneficial to humans (or a specific group of people), it is assumed to be useless and harmful. Cancer screening and other physical examination methods are also subject to this principle.

Cancer screening is a health care measure for healthy people. It is necessary to be extremely cautious, not only considering the impact on the health of the entire population, but also considering the cost-benefit and medical insurance issues. A cancer screening should be recommended by professional authorities and recognized by the government and commercial insurance. It requires evidence-based medicine to prove that screening is better than not screening.

The best evidence-based medicine comes from multiple well-designed randomized controlled trials with large enough samples. Due to the particularity of cancer screening, a fairly long observation period is also required - even the most effective cancer prevention measures take several years to see results.

After accumulating a certain amount of clinical trials, some research institutions and academic organizations will summarize and analyze these data. There are two important contents: one is to evaluate the quality of clinical trials, and the other is to conduct a meta-analysis of the summarized data.

Taking the USPSTF's opinion on colon cancer screening as an example, the current latest version of the opinion is based on a systematic review published in the Journal of the American Medical Association (JAMA) in 2021. In this systematic review, the authors collected colon cancer screening studies with a follow-up date up to March 2021.

The researchers first conducted a massive search and obtained 11,306 papers on colorectal cancer screening. After eliminating 10,804 papers that did not meet the requirements based on the titles and abstracts, 502 papers were included. After reading the full text of these 502 papers, the USPSTF expert team divided them into three categories, corresponding to three key questions:

Question 1: Is there any benefit of screening compared with no screening, including randomized controlled and non-randomized controlled trials;

Question 2: Using colonoscopy as the standard, how accurate are different screening methods, including stool examination and CT imaging?

Question three: Adverse reactions caused by screening, including the risk of death.

Regarding the issue of colonoscopy screening, which is of general concern, the recommendations are mainly based on two large-sample prospective cohort observations: one is a 24-year follow-up survey of medical staff including nurses and male doctors; the other is a shorter 8-year survey, which is based on the analysis of Medicare patient data. The results showed that colonoscopy screening reduces the risk of death from colon cancer by more than 60% (Adjusted Hazard Ratio, 0.32).

Based on the analysis of evidence, USPSTF marked the colon cancer screening recommendations for people aged 50-75 and 45-49 as A and B respectively. A means that USPSTF is very sure that screening can bring significant benefits, and B means that USPSTF is sure that screening can bring moderate to significant benefits. There are also C and D, corresponding to the reduction of certainty and recommendation, among which D means opposing a certain screening and believing that it will not bring benefits.

Different recommendation levels not only affect medical practice, but also, more importantly, are linked to medical insurance. For Class A recommended medical treatments, insurance companies are required to provide full coverage.

It should be pointed out that these recommendations are not static and may be updated every few years. If there is newer and better evidence that is inconsistent with the current recommendations, the previous opinions may be overturned. In October 2022, the New England Journal of Medicine (NEJM) published a European multicenter study that found that colonoscopy can reduce the incidence of colon cancer (hazard ratio 0.82, 95% confidence interval 0.7-0.93), but has no significant effect on the risk of death from colon cancer (hazard ratio 0.90, 95% confidence interval 0.64-1.16, it is generally believed that the confidence interval crossing 1 is not significant). It is not yet known whether this study will affect the next screening revision.

Before the official revision is published, doctors can still legally recommend these screening methods to patients. Some people may worry that this is not "evidence-based" enough, and believe that doctors should keep up with the latest medical advances. But in fact, individual doctors have limited energy, and not only is there endless medical information, but there is also endless new information. It is basically impossible for an individual to do the time-consuming and labor-intensive work of collecting, organizing, identifying and counting evidence mentioned above.

Other cancer screening opinions also have a similar process of generation, and they may also be revised or even overturned in the face of new evidence. This may make the public feel a little uneasy: it turns out that these screenings certified and recommended by authoritative organizations are uncertain. When it comes to health issues, we all want to get definite answers. This feeling is understandable, but it is not realistic. After all, the development of medicine requires time.

Fanpu has previously discussed the chaos in cancer screening. There are many reasons for this chaos, the main reason being the lack of recommendations from authoritative organizations and the lack of supporting education, training, medical insurance and other measures. The types of cancer and risk groups in different countries and regions are not the same, and copying the cancer screening opinions of other countries is not a solution. To achieve truly scientific and effective screening, we still have to start from the basics.

Reference Links

[1] https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening

[2] https://www.uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes/grade-definitions

[3] https://jamanetwork.com/journals/jama/fullarticle/2779987

[4] https://www.nejm.org/doi/full/10.1056/nejmoa1301969

[5] https://www.nejm.org/doi/full/10.1056/NEJMoa2208375

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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