Rethink the monies spent on cancer screening tests

Erik Peper, PhD and Richard Harvey, PhD

Cancer screening tests are based upon the rational that early detection of fatal cancers enables earlier and more effective treatments (Kowalski, 2021), however, there is some controversy.  Early screening may increase the risk of over diagnosis, treating false positives (people who did not have the cancer but the test indicates they have cancer) and potentially fatal treatment of cancers that would never progress to increase morbidity or mortality (Kowalski, 2021).

Today about $40 billion spent on colon cancer screening, $15 billion spent on breast cancer screening, and $4 billion spent on prostate cancer screening annually (CSPH, 2021). A question is raised whether the billions and billions of dollars spent on screening asymptomatic participants would be more wisely spent on promoting and supporting life style changes that reduce cancer risks and actually extend life span? That cancer screening is expensive does not mean no one should be screened. Instead, the argument is that the majority of healthcare dollars could be spent on health promotion practices and reserving screening for those people who are at highest risk for developing cancers.

What is the evidence that screening prolongs life?

Cancer screening tests appear correlated with preventing deaths since deaths due to cancers in the USA have decreased by about 28% from 1999 to 2020 (CDC, 2023a). Although cancer causes many of the deaths in the USA,  overall life expectancy has increased by less than 1% from 1999 to 2020. If cancer screening were more effective, the life expectancy should have increased more because cancer is the second leading cause of death (CDC, 2023b).  Consider also that deaths due to cancers may be coincident and or comorbid with other circumstances. For example, during the last four years, overall life expectancy in the USA has precipitously declined in part due to other causes of death such as the COVID pandemic and opioid overdose epidemic (Lewis, 2022). Decline in life expectancy in the USA has many contributing factors, including the ‘harms’ associated with cancer screening procedures. For example, perforations during colon cancer screening can lead to internal bleeding, or complications related to surgeries, radiotherapies or chemotherapies. Bretthauer et al., (2023) commented: “A cancer screening test may reduce cancer-specific mortality but fail to increase longevity if the harms for some individuals outweigh the benefits for others or if cancer-specific deaths are replaced by deaths from competing cause” (p. 1197).

Bretthauer et al. (2023) conducted a systematic review and meta-analysis of 18 long-term randomized clinical trials involving 2.1 million Individuals with more than nine years of follow-up reporting on all-cause mortality. They reported that“…this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy.”  

Following is a summary of Bretthauer et al. (2023) findings:

  • The only cancer screening with a significant lifetime gain (approximately 3 months) was sigmoidoscopy.
  • There was no significant difference between harms of screening and benefits of screening for:
    • mammography
    • prostate  cancer screening
    • FOBT (fecal occult blood test) screening every year or every other year
    • lung cancer screening Pap test cytology for cervical cancer screening, no randomized clinical trials with cancer-specific or all-cause mortality end points and long term follow-up were identified.

Potential for loss or harm (e.g., iatrogenic and nosocomial) versus potential for benefit and extended life

More than 35 years ago a significant decrease in breast cancer mortality was observed after mammography was implemented. The correlation suggested a causal relationship that screening reduced mortality (Fracheboud, 2004).  This correlation made logical sense since the breast cancer screening test identified cancers early which could then be treated and thereby would result in a decrease in mortality.

How much money is spent on screening that may  correlate with unintended harms?

The annual total expenditure for cancer screening is estimated to be between $40-$50 billion annually (CSPH, 2021).  Below are some of the estimated expenditures for common tests other than colorectal cancer screening, which arguably is costly; however, has potential benefits that outweigh potential harms.

What is the correlation between initiation of mammography and decrease in breast cancer mortality?

The conclusion that mammography reduced breast cancer mortality was based upon studies without control groups; however, this relationship could be causal or synchronistic.  The ambiguity of correlation or causation was resolved with the use of natural experimental control groups. Some European countries began screening 10 years earlier than other countries. Using statistical techniques such as propensity score matching when comparing the data from countries that initiated mammography screening early (Netherlands, Sweden and Northern Ireland) to countries that started screening 10 year later (Belgium, Norway and Republic of Ireland), the effectiveness of screening could be compared.

The comparisons showed no difference in the decrease of breast cancer mortality in countries that initiated breast cancer screening early or late. For example, there was no difference in the decrease of breast cancer mortality rates of women who lived in the Netherlands that started screening early versus those who lived in Belgium that began screening 10 years later, as is shown Figure 1 (Autier et al, 2011).

Figure 1. No difference in age adjust breast cancer mortality between the two adjacent countries even though breast cancer screening began ten years earlier in the Netherlands than in Belgium (graph reproduced from Autier et al, 2011).

The observations are similar when comparing neighboring countries: Sweden (early screening) to Norway (late screening) as well as Northern Ireland, UK  (early screening) compared to the Republic of Ireland (late screening). The systematic comparisons showed that screening did not account for the decrease in breast cancer mortality. To what extent could the decrease in mortality be related to other factors such as better prenatal and early childhood diet and life style, improved nutrition, reduction in environmental pollutants, and other unidentified  life style and environmental factors which improve immune competence?

A simplistic model to reduce the risk of cancers is described in the following equation (Gorter & Peper, 2011).

Cancer risk can be reduced, arguably by influencing risk factors that contribute to cancers as well as increasing factors to enhance immune competence. In the simple model above, ‘Cancer burden’ refers to the set of exposures that increase the odds of cancer formations. Categories include exposures to oncoviruses, environmental exposures (e.g., ionizing radiation, carcinogenic chemicals) as well as genetic (e.g., chromosomal aberrations, replication errors) and epigenetic factors (e.g., lifestyle categories related to eating, exercising, sleeping, and relaxing). In the model above, ‘Immune competence’ refers to a set of categories of immune functioning related to DNA repair, orderly cell death (i.e., processes of apoptosis), expected autophagy, as well as ‘metabolic rewiring,’ also called cellular energetics, that would allow the body to be able to reduce manage cancers from progressing (Fouad & Aanei, 2017) .

How do we examine the cancer burden/immune competence relationship?

Schmutzler et al., (2022) have suggested personalized and precision-medicine risk-adjusted cancer screening incorporating “… high-throughput “multi-omics” technologies comprising, among others, genomics, transcriptomics, and proteomics, which have led to the discovery of new molecular risk factors that seem to interact with each other and with non-genetic risk factors in a multiplicative manner.” The argument is that ‘profit-centered’ medicine could incorporate ‘multi-omics’ into risk-adjusted cancer screening as a way to reduce potential loss or harm due to other cancer screening procedures. Rather than simply screening for cancers using currently invasive or toxic procedures which may do more harm than good, consider more nuanced screening tests aimed at the so-called ‘hallmarks of cancer?’  For example, Hanahan (2022) suggests some technical targets for the multi-omics technologies. The following are some of the precision screening tests possible topersonalized medicine of 14 factors or processes related to:

  • cells evading growth suppression
  • non-mutational epigenetic reprogramming
  • avoiding immune destruction
  • enabling replicative immortality
  • tumor-promoting inflammation
  • polymorphic microbiomes
  • activating invasion and metastasis
  • inducing or accessing vasculature formation/angiogenesis
  • cellular senescence
  • genome instability and mutation
  • resisting cell death
  • deregulating cellular metabolism
  • unlocking phenotypic plasticity
  • sustaining proliferative signaling

Of the listed categories above, ‘phenotypic plasticity’ (cf. Feinberg, 2007; Gupta et al., 2019) suggests that lifestyle behaviors and environmental exposures play a role in cancer progression and regression.

Lifestyle and environmental factors can contribute to the development of cancers.

The 2008-2009 report from the President’s Cancer Panel appraised the National Cancer Program in accordance with the National Cancer Act of 1971 stated (Reuben, 2010):

Multiple research studies have shown that a healthy life style pattern is associated with decreased cancer risks and increased longevity. Lifestyle factors that have been documented to increase cancer risks in the United Kingdom (UK) as shown in figure 2.

Figure 2. Percentages of cancer cases in the UK attributable to different exposures. Adapted from Brown et al., 2018 and reproduced by permission from Key et al., 2020.

Similar findings have been reported by Song et al. (2016) from the long term follow-up of 126901 adult health care professionals.  People who never smoked, drank no alcohol or moderate alcohol (< 1 drink/d for women; < 2 drinks/d for men}, had a body-mass index (BMI) of at least 18.t but lower than 27.5, did weekly aerobic physical activity of at least 75 vigorous-intensity minutes or 150 150 moderate-intensity minutes compared to those who smoked, drank, had high BMI and did not exercise had nearly half the cancer death rate. Song et al (2016) concludes:

Said another way, primary prevention should remain a priority for cancer control.

Given that many cancers are related to diet, environment and lifestyle, it is estimated that 50% of all cancers and cancer deaths could be prevented by modifying personal behavior. Thus, the monies spent on screening or even developing new treatments could better be spent on prevention along with implementing programs that promote a healthier environment, diet and personal behavior (AACR, 2011).

What can be done? Addressing systems not symptoms

From a ‘systems perspective,’ the first step is to reduce the cancer burden and carcinogenic agents that occur in our environment such environmental pollution (Turner et al., 2022). In many cases, governmental regulations that reduce cancer risk factors have been weakened, delayed, and contested for years through industry’s lobbying. It often takes more than 30 years after risk factors have been observed and documented before government regulations are successfully implemented, as exemplified in the battle over tobacco or, air pollution regulations related to particulates from burning fossil fuels (Stratton et al, 2001). 

Sadly, we cannot depend upon governments or industries to implement regulations known to reduce cancer risks. More within our control is implementing lifestyle changes that enhance immune competence and promote health. 

Implement a healthy life style that enhances immune competence and, supports health and well-being

Paraphrasing a trope of what some physicians may state: ‘Take two pills, and call me in the morning. Oh, and eat well, exercise, and get good rest.’ Broadly stated, the following are some controllable lifestyle behaviors that can decrease cancer risks and promotes health. Implementing environmental and lifestyle changes are very challenging because they are highly related to socio economic factors, cultural factors, industry push for profits over health, and self-care challenges since there are no immediate results experienced by behavior and lifestyle changes.

In many cases, the effects of harmful life-style and environment factors are only observed twenty or more years later (e.g., diabetes, lung cancer, cirrhosis of the liver). The individual does not experience immediate benefits of lifestyle changes thus it is more challenging to know that your healthy life style has an effect.  The process is even more complex because in most cases it is not a single factor but the interaction of multiple factors (genetics, lifestyle, and environment). The complexity of causality so often conflicts with the simplistic research studies to identify only one isolated risk factor. Instead of waiting for the definitive governmental guidelines and regulations, adopt a ‘precautionary principle’ which means do not take an action when there is uncertainty about its potential harm (Goldstein, 2001).  Do not wait for screening; instead, take charge of your health and implement as many of the following behaviors and strategies to enhance immune competence and thereby reduce cancer risks.

Many studies have suggested that eating organic foods and in particular more fruits and vegetable such as a Mediterranean diet is associated with increased health and longevity. Similarly, people who eat do not eat highly-processed or ultra-processed foods have better health status (Van Tulleken, 2023).   For example, In the large prospective study of 68, 946 participants, adults who consumed the most organic fruits, vegetables, dairy products, meat and other foods had 25% fewer cancers when compared with adults who never ate organic food (Baudry et al., 2018; Rabin, 2018). Similarly, many studies have reported that those who adhere consistently to a Mediterranean diet have a significantly lower incidence of chronic diseases (such as cardiovascular diseases, diabetes, etc.) and cancers compared to  those who do not adhere to a Mediterranean diet (Mentella et al., 2019).

Air pollution and the exposure to airborne carcinogens are a significant risk factor for cancers as illustrated by the increased cancer rates among smokers. In the USA, the reduction of smoking has significantly decreased the lung cancer deaths (US Department of Health and Human Services, 2014).

Many studies have documented that people who exercise regularly and are otherwise non–sedentary but are active their entire lives have the lowest risk for breast cancers and colon cancers. Women who exercise 3 hours a week or more have a 30-40% lower risk of developing breast cancer (NIH NCI, 2023).  The NIH National Cancer Institute summary concludes that exercises also significantly benefited the following cancer survivors (NIH NCI, 2023):

  • Breast cancer: In a 2019 systematic review and meta-analysis of observational studies, breast cancer survivors who were the most physically active had a 42% lower risk of death from any cause and a 40% lower risk of death from breast cancer than those who were the least physically active (Spei et al, 2019). 
  • Colorectal cancer: Evidence from multiple epidemiologic studies suggests that physical activity after a colorectal cancer diagnosis is associated with a 30% lower risk of death from colorectal cancer and a 38% lower risk of death from any cause (Patel et al., 2019). 
  • Prostate cancer: Limited evidence from a few epidemiologic studies suggests that physical activity after a prostate cancer diagnosis is associated with a 33% lower risk of death from prostate cancer and a 45% lower risk of death from any cause ((Patel et al., 2019). 
  • Implement stress management. 

Chronic stress may reduce immune competence and increase the risk of cancers as well as hinders healing from cancer treatments (Dai et al., 2020). The results of numerous studies have shown that implementing stress management spractices uch as  Cognitive-behavioral stress management (CBSM) improves mood and lowers distress during treatment and, is also associated with longer survival compared to control groups in the 8-15 year follow up (Stagl et al., 2015).

The International Agency for Research on Cancer (IARC) reports that, when the human circadian clock is disrupted, the likelihood of developing cancers, including lung cancers, intestinal cancers, and breast cancers, dramatically increases (Huang, et al.,  2023). Go to bed at the same time and, have about 8 hours of sleep. As much as possible avoid night shifts at work along with frequent jet lag as that highly disrupts the circadian rhythm.

Absence of social support, feeling lonely and socially isolated tends reduces immune competence and increases cancer mortality risk while having more social support satisfaction is associated with lower mortality risks (Salazaor et al., 2023; Boen et al., 2018).  Meta-analysis of 148 studies (308,849 participants) found that that on the average there is a 50% increased likelihood of survival for participants with stronger social relationships (Holt-Lunstad et al., 2010).

Having meaning and purpose make each moment worth living and may contribute to improving immune function and possible cancer survival (LeShan, 1994; Rosenbaum & Rosenbaum, 2023).

Summary

See also the following blogs:

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