JOURNAL OF WOMEN'S HEALTHVolume 7, Number 1, 1998Mary Ann Liebert, Inc.

Review

Colorectal Cancer in Women:An Underappreciated but Preventable Risk

JOANNE M. DONOVAN, M.D., Ph.D.,1 and SAPNA SYNGAL, M.D., M.P.H.1-2

ABSTRACT

Colorectal cancer is the third most common non-skin malignancy in women, after breast andlung cancer. Although approximately 40% of the 65,000 women diagnosed each year eventu-ally die of the disease, colon cancer is highly curable when diagnosed at an early stage. More-over, because the majority of colon cancers arise in previously benign colonie polyps, thereis a substantial period, up to several years, in which removal of polyps can reduce the riskof colon cancer. Recently, the United States Preventive Task Force recommended universalscreening for colon cancer after age 50. Strong evidence from randomized controlled trialsand case-control studies supports use of annual testing for occult blood in stool and flexiblesigmoidoscopy every 5-7 years. Although the risk of colon cancer is similar in men andwomen, women frequently have the perception that colorectal cancer is a man's disease. Par-tially in consequence, women are less likely than men to undergo screening sigmoidoscopy.Further barriers include primary care providers' lack of awareness of updated guidelines andpatients' lack of compliance with multiple screening tests and their fear of discomfort. Be-cause the risk of colorectal cancer can be reduced by up to 75% in those who undergo screen-

ing and subsequent surveillance to remove further polyps, it is crucial that women be tar-geted to undergo screening tests for colorectal cancer.

Cancers of the colon and rectum account tality from colorectal cancer in women is un-

for more than 65,000 new cases and 24,000 derappreciated by the general public. This se-

deaths in women each year.1 Colorectal cancer rious level of misperception is indicated by theis the third most common type of tumor found high number of lay press articles about breastin women, following breast and lung cancers, cancer compared with those about colorectalFor a woman currently aged 65 years, the risk cancer. Fortunately, mortality from colorectalof death from colorectal cancer over the next 20 cancer appears to be decreasing, possibly be-years is about equal to the risk of death from cause of lifestyle changes and earlier detectionbreast cancer.2 The high incidence of and mor- by screening tests. Furthermore, colorectal can-

department of Medicine, Brockton/West Roxbury VA Medical Center, and Brigham and Women's Hospital, Har-vard Medical School, Boston, Massachusetts.

2Dana-Farber Cancer Institute, Boston, Massachusetts.This work was supported in part by research funding from the Veterans Administration.This review updates a presentation made at the Fifth Annual Congress on Women's Health, Washington, DC, June

23-25, 1997.

45

46 DONOVAN AND SYNGAL

cer mortality can be reduced even more by theeffective use of currently available screeningand surveillance modalities.

The highest incidence rates of colorectal can-

cer are seen in the developed world, includingNorth America, western Europe, and Aus-tralia.3 Data from epidemiologic studies haveindicated that risk factors for colorectal cancer

include a high-fat, low-fiber diet, excessive use

of alcohol, sedentary lifestyle, and older age.3-5People with a family history of colorectal can-

cer, a personal history of colonie polyps, andinflammatory bowel disease are also at higherrisk for developing colorectal cancer.

Screening and surveillance for colorectal can-cer are facilitated by two key factors about thebiology of the disease. First, the vast majorityof malignant colorectal cancers arise from be-nign adenomatous polyps. Invasive colorectalcancer is preceded by several transformations,from normal to adenomatous mucosa to inva-sive carcinoma, a process that evolves over

years.6 The long lag period provides ample op-portunity for detecting and removing prema-lignant lesions and thereby preventing cancer.

The second major point about the biology ofcolorectal cancer is that survival is critically de-pendent on the tumor stage at detection. Thedistribution of colorectal cancer by stage inwomen and men is similar. Detecting colorec-tal cancer at a localized stage, when it is lim-ited to the mucosa, is associated with a 5-yearsurvival rate of >90%. In contrast, 5-year sur-

vival rates for colorectal cancer that has spreadto lymph nodes or adjacent organs fall to ap-proximately 60%, and for metastatic cancer,survival rates are <10%.1 Colorectal cancers are

relatively insensitive to chemotherapy or ra-

diotherapy, which is reflected in the low sur-

vival rates associated with metastatic disease.Thus, to decrease colorectal cancer deaths, it isessential to detect tumors at early, curablestages or, alternatively, to interrupt the polyp-to-cancer sequence.

There is strong evidence that two screeningtests, fecal occult blood testing (FOBT) and sig-moidoscopy, can reduce mortality from col-orectal cancer. A trial of annual FOBT testingand evaluation of abnormal tests withcolonoscopy, involving more than 46,000 pa-tients at the University of Minnesota, showed

a 33% reduction in colorectal cancer mortalityover 13 years.7 Furthermore, the screenedgroup showed a shift to detection of colorectalcancer at an earlier stage of cancer comparedwith controls. Several other controlled trialshave confirmed the findings of this study.8'9

Case-control studies have indicated that flex-ible sigmoidoscopy can also help reduce mor-

tality from colorectal cancer.10'11 Sigmoidoscopyhas high sensitivity for early stage cancers andprecursor adenomas.12 A landmark study re-

vealed a 70% reduction in distal colorectal can-

cer mortality but no reduction in risk of deathfrom proximal colon cancer in individuals whohad undergone sigmoidoscopy, compared withcontrols.10 The reduction in mortality in only thesegment of the colon that was within reach ofthe sigmoidoscope was powerful evidence thatthe risk reduction was directly related to sig-moidoscopy. Several other case-control studieshave revealed similar results.11'13

FOBT and sigmoidoscopy are complemen-tary tests. Reported sensitivities of FOBT rangefrom 38% to 92%.14 The potential effectivenessof sigmoidoscopy is limited by the length ofthe instrument used and ranges from 20% forrigid sigmoidoscopy15 to 40%-60% for a 60-cmflexible sigmoidoscope.16-17 A controlled trialcomparing sigmoidoscopy alone with sigmoi-doscopy combined with FOBT confirmed thatmortality was lower in the group undergoingboth tests than one test alone.8 Thus, to maxi-mize detection of colorectal cancer, both testsshould be used.

Further evidence that we can prevent col-orectal cancer comes from studies of patientswho have previously had colonie adenomas.Surveillance colonoscopy and polypectomyevery 1-3 years is effective in reducing col-orectal cancer incidence in those individuals at

high risk for cancer from having a history ofadenomatous polyps.6'18

Cost effectiveness analyses have shown thatcolorectal cancer screening costs are similar tocosts of other screening modalities, includingbreast and cervical cancers. Colorectal cancer

screening costs <$20,000 per year of life saved,well within an acceptable range of cost effec-tiveness by United States health standards.14

In February 1997, based on the strength ofavailable evidence, an expert panel made rec-

COLORECTAL CANCER IN WOMEN

ommendations for individuals at average riskfor colorectal cancer. The guidelines, whichhave been endorsed by the American CancerSociety and all major gastroenterology soci-eties,14 are that:

• all persons over 50 years old should un-

dergo annual FOBT, with evaluation of theentire colon in patients with positive tests,preferably by colonoscopy

• all persons over 50 should undergo flexiblesigmoidoscopy every 5 years.

Recommendations for those at increased riskfor colorectal cancer, because of either a per-sonal history of adenomatous polyps, colorec-tal cancer, or inflammatory bowel disease or a

family history of colorectal cancer, include pe-riodic surveillance of the entire colon (either bycolonoscopy or barium enema and sigmoi-doscopy).

Thus, there is ample evidence that colorectalcancer incidence and mortality in women couldbe greatly reduced through appropriate screen-

ing and surveillance for colorectal cancer andthat such screening is cost effective. Despite thestrength of the evidence available, however,most American women are not currentlyscreened for colorectal cancer. The BehavioralRisk Factor Surveillance System and the Na-tional Health Interview Survey are two largestudies of the use of screening tests by the U.S.population. Both instruments revealed thatcompliance rates for colorectal cancer screen-

ing were much lower than for other can-

cers.19'20 In women >50 years old, compliancerates for FOBT and sigmoidoscopy were

27%-40% and 7%-24%, respectively. In com-

parison, 49%-54% of women >50 had under-gone mammography within 2 years, and >57%of women had been appropriately screened forcervical cancer. In addition, although aware-ness of the availability of the FOBT and sig-moidoscopy was higher in women than in men,men were more likely than women to undergoboth tests.21

Studies reveal that awareness of the risk ofcolorectal cancer is low among Americanadults.21'22 Further barriers include primarycare providers' lack of awareness of updated

47

guidelines and patient's lack of compliancewith multiple screening tests, as well as theirfear of discomfort. As for other preventive ser-

vices, lack of insurance coverage is a barrier touniversal compliance. Factors related to higherrates of compliance with screening includeknowledge of colorectal cancer, higher educa-tional level, and having friends or relativeswith the disease.21 Health care providers can

play a major role in enhancing compliance.Good communication between patients andtheir health care providers and effective use ofeducational materials can greatly enhance pa-tients' participation and satisfaction.23-25

Groups examining women's health havetended to focus on breast, ovarian, and cervi-cal cancers and not colon cancer even thoughthey examine compliance with nonreproduc-tive health measures, such as blood pressureand cholesterol screening. Although the risk ofcolorectal cancer is similar in men and women,there is a perception that it is a man's disease.

To obtain the estimated number of deathsthat could be prevented by universal screeningof women, we multiplied the current numberof deaths for breast, colon, and cervical cancers

by conservative estimates for the reduction inmortality by screening—about 40% for breastcancer, 67% for colon cancer, and 90% for cer-

vical cancer. Lung cancer is excluded becauseearly detection by screening has not beenshown to be efficacious and is not generally rec-

ommended. Although breast cancer is more

common in women, the effectiveness of screen-

ing for breast cancer is limited by the fact thatit only detects cancer at an early stage and is

Potential lives saved by cancer surveillance:20,000 "I

Breast Colon Cervical

FIG. 1. Estimate of the number of deaths that could beprevented if women were universally screened for breast,colon, and cervical cancers. Figures are derived by mul-tiplying the number of women dying of each disease1 bythe estimated reduction in mortality by screening.

48 DONOVAN AND SYNGAL

not a means to prevent cancer. Screening ishighly effective for cervical cancer, but the in-cidence is low. The net result is that screeningfor colon cancer is estimated to save as manywomen's lives as screening for breast cancer

(Fig. 1).Colorectal cancer is common in both women

and men, accounting for the second largestnumber of cancer deaths overall. For 1997, theAmerican Cancer Society26 estimated that some

131,000 new cases would be diagnosed and that55,000 people, nearly half of them women,would die. The message for both clinicians andpatients is that mortality from colorectal can-

cer is largely preventable. We believe that en-

suring that women receive appropriate screen-

ing for colorectal cancer should be a major goalfor improving women's health.

REFERENCES

1. National Cancer Institute. SEER Cancer Statistics Re-view, 1973-1991: Tables and graphs, NIH Pub. No.94-2789. Bethesda, MD: National Institutes of Health,1994.

2. National Cancer Institute. SEER Cancer Statistics Re-view, 1973-1989, NIH Pub. No. 92-2789. Bethesda,MD: National Institutes of Health, 1992.

3. Potter JD, Slattery ML, Bostick RM, Gapstur SM.Colon cancer: A review of the epidemiology. Epi-demiol Rev 1993;15:499.

4. Howe GR, Benito E, Castelleto R, et al. Dietary intakeof fiber and decreased risk of cancers of the colon andrectum: Evidence from a combined analysis of 13case-control studies. J Nati Cancer Inst 1992;84:1887.

5. Willett WC, Stampfer MJ, Colditz GA, Rosner BA,Speizer FE. Relation of meat, fat and fiber intake tothe risk of colon cancer in a prospective study amongwomen. N Engl J Med 1990;323:1664.

6. Winawer SJ, Zauber AG, Ho MN, et al. Prevention ofcolorectal cancer by colonoscopic polypectomy. NEngl J Med 1993:329:1977.

7. Mandel JS, Bond JH, Church TR, et al. Reducing mor-

tality from colorectal cancer by screening for fecal oc-cult blood. Minnesota Colon Cancer Control Study. NEngl J Med 1993;328:1365.

8. Winawer SJ, Flehinger BJ, Schottenfeld D, Miller DG.Screening for colorectal cancer with fecal occult bloodtesting and sigmoidoscopy. J Nati Cancer Inst1993;85:1311.

9. Kronborg O, Fenger C, Olsen J, Jorgensen OD, Son-dergaard O. Randomised population study of screen-

ing for intestinal cancer with Hemoccult-II. UgeskrLaeger 1997;159:4977.

10. Selby JV, Friedman GD, Quesenberry CP, Weiss NS.A case-control study of screening sigmoidoscopy and

mortality from colorectal cancer. N Engl J Med1992:326:653.

11. Newcomb PA, Norfleet RG, Storer BE, Surawicz T,Marcus PM. Screening sigmoidoscopy and colorectalcancer mortality. J Nati Cancer Inst 1992;84:1572.

12. Ransohoff DF, Lang CA. Sigmoidoscopic screening inthe 1990s. JAMA 1993;269:1278.

13. Muller AD, Sonnenberg A. Protection by endoscopyagainst death from colorectal cancer. Arch Intern Med1995:155:1741.

14. Winawer SJ, Fletcher RH, Miller L, et al. Colorectalcancer screening: Clinical guidelines and rationale.Gastroenterology 1997;112:594.

15. Devesa SS, Chow WH. Variation in colorectal cancerincidence in the United States by subsite of origin.Cancer 1993;71:3819.

16. Selby JV, Friedman GD. U.S. Preventive Task Force.Sigmoidoscopy in the periodic health examination ofasymptomatic adults. JAMA 1989;261:594.

17. Selby JV, Friedman GD, Collen MF. Sigmoidoscopyand mortality from colorectal cancer: The Kaiser Per-manente Multiphasic Evaluation Study. J Clin Epi-demiol 1988:41:427.

18. Muller AD, Sonnenberg A. Prevention of colorectalcancer by flexible endoscopy and polypectomy. Acase control study among 32,702 veterans. Ann InternMed 1995:123:904.

19. Centers for Disease Control and Prevention. MMWRFeb 9,1996.

20. Anderson LM, May DS. Has the use of cervical, breastand colorectal cancer screening increased in theUnited States? Am J Public Health 1995;85:840.

21. Brown ML, Potosky AL, Thompson GB, Kessler LG.The knowledge and use of screening tests for col-orectal and prostate cancer: Data from the 1987 Na-tional Health Interview Survey, Prev Med 1990;19:562.

22. Bostick RM, Sprafka JM, Virning BA, Potter JD.Knowledge, attitudes and personal practices regard-ing prevention and early detection of cancer. PrevMed 1993;22:65.

23. Myers R, Trock BJ, Lerman C, Wolf T, Ross E, Eng-strom PF. Adherence to colorectal cancer screening inan HMO population. Prev Med 1990;19:502.

24. McCarthy BD, Moskowitz MA. Screening flexible sig-moidoscopy: Patient attitudes and compliance. J GenIntern Med 1993;8:120.

25. Kelly RB, Shank JC. Adherence to flexible sigmoid-oscopy in asymptomatic patients. Med Care 1992;30:1029.

26. American Cancer Society. Colon and rectum cancer.Cancer Facts & Figures—1997. Atlanta, GA: Ameri-can Cancer Society, 1997.

Address reprint requests to:Joanne A4. Donovan, M.D., Ph.D.

Brockton/West Roxbury Department ofVeterans Affairs Medical Center

1400 VFW ParkwayBoston, MA 02132