Colorectal cancer (CRC) remains a major health challenge in the United States and throughout the developed world. Eminently preventable and treatable in most situations, the successful management of CRC as a public health problem requires a comprehensive strategy of risk assessment, prevention, early detection, effective treatment, awareness and, most importantly, access to quality medical care. Sadly, here in the United States, we continue to lag in many of these areas, thus creating an environment where the impact of CRC remains greater than we should otherwise expect.
For the purposes of this discussion, we need to recognize that CRC can have different cellular origins. This article will focus for the most part on those that are the most common, namely adenocarcinomas of the colon and rectum. Anal carcinoma is also a digestive tract cancer and merits the attention of clinicians who care for people who are genotypical female. Increasing incidence mandates medical professionals understand the need to screen and appropriately manage anal cancers, however, space does not allow a detailed review in this overview of CRC.
We have been successful in reducing rates of CRC incidence and deaths – especially in women – over the past several decades in the United States. More recently, the onset and persistence of the COVID-19 pandemic has impaired our efforts to effectively screen for CRC (Bakouny et al., 2021). How this will affect the long-term incidence and mortality from CRC remains to be seen. Unfortunately, we do expect some slippage from the progress that we had achieved to date as a result of decreased screening opportunities over the past two years, which will likely continue for an unknown period.
Looming over all these efforts are the future unknowns, such as how our health systems will be restructured, whether primary care will evolve in a helpful or harmful way as its workforce undergoes a fundamental shift, and whether consumers will still have an organized process to engage them in CRC screening or whether new technologies will emerge to help them manage their individual care.
We will also need to address the past and persistent scourge of health inequities that have led to significant differences in access and outcomes for CRC that have evolved since the 1980s and 1990s, when we developed screening and treatment strategies that decreased incidence and mortality in the majority population (Mandel et al., 1993).
In addition, over the past several years, we have come to recognize that younger people are seeing an increased risk of CRC as reflected in an increase in the rates of CRC in ages below 50 (Siegel et al., 2017; Siegel et al., 2009). This has led to both the American Cancer Society (Wolf et al., 2018) and the United States Preventive Services Task Force (USPSTF, 2021) recommending the age of onset for CRC screening for people at average risk be reduced to starting at age 45 instead of the previously recommended age of 50 years old.
CRC Incidence and Mortality in Women
The American Cancer Society estimates that in 2022 there will be 70,340 new cases of invasive CRC in women in the United States, accounting for 8% of the 934,870 newly diagnosed invasive cancers in the nation this year. 52,140 will be found in the colon, and 18,200 will be rectal cancers (Siegel et al., 2022).
By convention, we refer to all of these cancers as a single diagnosis for the purposes of this discussion, since frequently the site of origin of the tumor is not specific. In addition, the term “colon cancer” is frequently used to include rectal cancers, possibly diminishing the importance of this primary site of disease.
CRC is also the third most common cause of cancer deaths in women, accounting for 24,180 or 8% of the expected 287,270 deaths in 2022 from invasive cancer (Siegel et al., 2022). While the total number of deaths show a greater difference in men (28,400) compared to women (24,180), it is always important to remember that total numbers are not an accurate reflection of the burden of cancer incidence and mortality. The rate of incidence or deaths per 100,000 people is a more accurate and consistent reflection of the impact of any given cancer on the various measured populations (e.g., race, sex, and geographic location among other measures) at any particular point in time or over a period of time.
Anal cancers are another important part of the discussion of female cancers of the digestive tract. Although of a different pathologic origin, as mentioned previously (squamous cell vs. adenomatous/epithelial), their incidence is increasing. Although found in both men and women, the preponderance of anal cancers are anticipated to be diagnosed in women in 2022 (6,290 compared to 3,150) and a similar preponderance of deaths are in women (930 compared to 740) (Siegel et al., 2022).
The trends in incidence and mortality of typical CRC in women in the United States show a very interesting pattern, one for which there is neither a simple or agreed-upon explanation. Nonetheless, the observation is intriguing.
As shown in Figure 1, the incidence rates of CRC per 100,000 men in the United States increased slightly from 1975 through the mid-1980s, then began a continuing decline from the mid-1980’ to the present day. Although the pattern for CRC is similar for women, the observed incidence rates/100,000 for CRC are decidedly lower (Cancer Statistics Center, 2022).
However, there is a much more striking difference in the pattern of mortality in CRC for women, which is uniquely different from that seen in men. Figure 2 shows that CRC mortality rate/100,000 in men increased from 1930 to 1the late 1940s, remained strikingly stable through the mid-1980s, then began a significant and continuing decline to the present (Cancer Statistics Center, 2022).
One sees a much different sequence for women: similar to the pattern in men (not to ignore that the rate of death was higher in women than men in the 1930s), rates of death from CRC in women increased over the same period through the mid-1940s. However, unlike in men where the rates of death stabilized at that point, the death rates/100,000 for CRC in women began to show a significant, prolonged and continuing decline from the mid-1940s to the present day, without a substantial increase or decrease in rates of death for women in the mid-1980s, when the early detection of CRC became a generally accepted and effective strategy to reduce the burden of mortality from CRC.
There is no simple explanation for this observation. Possible explanations could include hormone replacement therapies, which have demonstrated reduced CRC morality in randomized trials (Writing Group for the Women’s Health Initiative Investigators, 2002) or NSAIDS such as low-dose aspirin may reduce CRC mortality (Jacobs et al., 2005). However, these were not common interventions in the mid-1940s. Consequently, one can only speculate about the explanation for this observation.
The reality is that we do not know why or how this happened. What we can say, however, is that the phenomenon is real, and understanding how this came about could offer important information about reducing the mortality and impact of CRC on populations throughout the world.
Equity
There are striking differences in the incidence and mortality rates of colorectal cancer in women of different ethnic heritages and residence in the United States.
According to the American Cancer Society, the overall age-adjusted incidence rate of colorectal cancer in women in the United States is 31.6/100,000. For Non-Hispanic White women, the rate is 31.3/100,000, while for Black women it is 37.1, for American Indian/Alaska Native it is strikingly high at 43.9 and for Hispanic/Latino women it is much lower at 27.6. Asian/Pacific Islander women have the lowest CRC incidence rate of 24.6 when compared to the general female population in the United States (Siegel et al., 2022).
Similar trends are also observed for mortality in colorectal cancer in women: for women of all races/ethnicities the age-adjusted mortality rate is 11.3/100,000, and for White women, it is also 11.3. However, for Black women, the mortality rate is increased to 14.8, and for American Indian/Alaska Native the age-adjusted mortality rate is 14.4. Mortality rates for colorectal cancer in Hispanic/Latino women are lower at 8.5, while Asian/Pacific Islander women have the lowest mortality rate of all groups at 7.9/100,000 (Siegel et al., 2022).
Interestingly, these differences in outcomes between racial groups were not always the case. For example, the mortality rates for colorectal cancer in Black and White women were essentially the same in 1975. Over time, the gap widened as the mortality rates in White women continued to decline through the 2015-2018 time period. Interestingly, there was a slight increase in colorectal cancer mortality rates in Black women from 1975 through the early 1990s, when it then began to decline. Although the gap has diminished more recently, it does persist to an unacceptable degree (Giaquinto et al.).
A detailed review of the reasons for these differences in incidence and outcomes between different ethnic/racial groups is beyond the scope of this paper. However, systemic and systematic differences in social, educational and place of residence factors among various population groups have been cited, especially those that affect access to care. Access to quality screening and treatment clearly impact outcomes in incidence and mortality for CRC and must be addressed if we are to substantially decrease the burden of CRC for all men and women in the United States and elsewhere.
Another important observation – which applies to both men and women– is that there have been significant increases in the incidence of CRC in people younger than 50. One of the recent reports on this acceleration of incidence in young people in the United States was in 2017 (Siegel et al., 2017). Subsequently, there has been increasing focus on this phenomenon, especially as it applies to the evaluation of symptoms in these age cohorts.
Although women have had a lower incidence of CRC from age 40-49 compared to men, their rates of earlier onset colorectal cancer have also been rising over the past 20 years for which data is available (Siegel et al., 2017). It is critically important that clinicians caring for women (and men) who are younger than age 45 (the currently recommended age for the onset of CRC screening in people at average risk) pay genuine attention to any sign or symptom that might present in that population.
Notwithstanding that symptoms consistent with CRC are less likely to be associated with CRC in someone under the age of 45, clinicians should nonetheless not dismiss these symptoms as incidental and arbitrarily rule out CRC as an underlying cause.
Screening
There are no differences in screening recommendations offered to people at average risk of developing colorectal cancer based on gender determination at birth. However, it is important for all health professionals to be aware of the guidelines offered by the United States Preventive Services Task Force (USPSTF et al., 2022) and the American Cancer Society (Wolf et al., 2018) among others.
There are a number of acceptable screening options available, including colonoscopy, fecal immunochemical tests and laboratory analysis of stool samples for genomic alterations. (Wolf et al., 2018). Early detection through blood tests analyzing circulating DNA fragments are now reaching the marketplace, and their longer-term application and impact on CRC identification and mortality in large, typical population-based settings remains to be determined.
No matter which test is used, it is important that all clinicians who see women for routine care include discussions and recommendations for colorectal cancer screening as part of their standard care procedures. Evolving healthcare systems must also develop routine programmatic efforts to address colorectal cancer screening for those consumers who are followed in those programs.
Although the COVID pandemic has impacted all cancer screenings (Chen et al., 2021), it is necessary for clinicians to avoid inappropriate delays in CRC screening, especially for those at higher risk (for example, family history, identified inherited genetic conditions, prior personal history of polyps or inflammatory bowel disease). Although there may currently be difficulty in getting a timely colonoscopy screening for colorectal cancer in some communities, it is important to remember that alternative tests exist and are still useful in diagnosing advanced polyps and early-stage CRC, where treatment is less complex and outcomes better than the alternative of waiting until common CRC screening tests such as a colonoscopy can be scheduled.
Looking Ahead
Colorectal cancer remains a leading cause of cancer incidence and mortality in the United States. Considerable work remains to be done if we are to continue to build on past successes in reducing the incidence and mortality of this disease. CRC is both preventable and treatable at early stages when organized efforts are made to educate the public regarding the need to engage in preventive behaviors, to get screened regularly, and to seek medical attention if symptoms occur.
Those who care for people identified as female gender at birth must make every effort to include colorectal cancer screening and symptom evaluation a top priority for their patients. Special recognition of symptoms in younger people in the face of rising incidence in this age group is also an important new lesson that we must all incorporate as we care for our patients.
Going forward, we are currently seeing the early rollout of newer blood-based early detection tests for colorectal and other cancers. Over time, this technology will improve and hopefully provide another effective option to further reduce the burden of cancer in our populations at risk. In the meantime, an adage that has served us well is that the best test for the early detection and prevention of CRC is the test that a patient/consumer will get.
There is much to be done to reduce the incidence and mortality of colorectal cancer. We need to implement those strategies we already know are effective in improving population outcomes. We must improve access to care and reduce inequities in cancer detection and treatment, including not only those based on racial, ethnic and gender identity but also be mindful that access based on education, insurance status and urban/rural location also play an important role. We need to improve our identification of those at high risk and bring them into a more intensive surveillance program if we are to achieve our goals. Going forward, as our health care systems evolve, we must find new approaches to reach out, educate and engage younger groups and embrace the challenges that will occur as our primary care models undergo a fundamental change in how primary and preventive care is delivered.
Together, through practice, awareness and commitment, we can decrease the impact of CRC for everyone, no matter what the challenges may be. If we see those challenges as opportunities, we can actually improve the care we provide to all and reduce the impact of a disease that is eminently preventable and treatable for so many who look to us for their healthcare.
References
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Dr. J. Leonard Lichentfeld
Dr. Lichtenfeld is a board-certified medical oncologist who is currently Chief Medical Officer of Jasper Health, Inc. He recently completed 19 years of service with the American Cancer Society, including as Deputy Chief Medical Officer. He serves on the board of CancerCare. Dr. Lichtenfeld is a graduate of the University of Pennsylvania and Hahnemann Medical College. His postgraduate training was at Temple University Hospital in Philadelphia, Johns Hopkins University School of Medicine and the National Cancer Institute in Baltimore.
