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Colorectal cancer screening in elderly patients: When should be more useful?
Cancer Treatment Reviews (2007) 33, 528– 532
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/ctrv
CONTROVERSY
Colorectal cancer screening in elderly patients: When should be more useful? Lara Maria Pasetto *, Silvio Monfardini Istituto Oncologico Veneto, IRCCS: Medical Oncology 2nd, Via Gattamelata 64, 35128 Padova, Italy Received 21 February 2007; received in revised form 10 April 2007; accepted 15 April 2007
KEYWORDS Elderly; Screening; Colorectal cancer
Summary Current guidelines endorse colon cancer screening every 5–10 years in persons over 50 years of age. However, there is no consensus regarding what age is appropriate to stop screening. Prior history of neoplasia seems to be a strong risk factor for colorectal neoplasia development in elderly people and should be considered when deciding the need for continuing screening/surveillance, however, clinical judgment of comorbidities is still required to individualize screening practice. Screening colonoscopy in very elderly persons (aged P80 years), i.e. should be performed only after careful consideration of potential benefits, risks and patient preferences. The aims of this paper are to: (1) determine the best type of colorectal cancer screening (faecal occult blood testing, flexible sigmoidoscopy, double-contrast barium enema and colonoscopy) and its association with age and health status among elderly veterans and (2) describe the outcomes of colorectal cancer screening among older veterans who have widely differing life expectancies (based on age and health status). c 2007 Elsevier Ltd. All rights reserved.
Introduction
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer deaths in North America. The incidence, that is approximately 650,000 cases per year worldwide and 30,000 in Italy, has increased in recent years while the mortality, that was approximately of 278,446 male and 250,532 female cases per year worldwide in 2002 and 9061 male and 7909 female * Corresponding author. Tel.: +39 049 8215931; fax: +39 049 8215932. E-mail addresses: [email protected] (L.M. Pasetto), [email protected] (S. Monfardini).
cases in Italy in the same year, has decreased or stabilised.1 In persons over 85 years, CRC constitutes, one third of all neoplasms with 70% of patients aged 65 years or older.2 Particularly, in persons >65 years old, the incidence of colon cancer is about 120 new cases per 100,000 inhabitants per year (and in persons >75 years old is about 200/100,000 inhabitants per year) and mortality is about 90 per 100,000 inhabitants per year.3 The time from the first symptom to the first medical consultation in the elderly is so long and it is about 113.4 days (16.2 weeks) for rectal cancer and 88.9 days (12.7 weeks) for colonic cancer. The time from first examination to treatment is 154.0 days (22.0 weeks) for rectal cancer and 135.1 days (19.3 weeks) for colonic cancer.4 Because of the dimension and the gravity of the
0305-7372/$ - see front matter c 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.ctrv.2007.04.004
Colorectal cancer screening in elderly patients: When should be more useful? problem, current guidelines recommend CRC screening for all persons 50 years or older, properly to anticipate the time of diagnosis, but at this moment there is no specific age limit above which screening is not recommended. Probably for this reason, nowadays, the number of screening colonoscopies for CRC and its precursor lesions (based on the estimate of the time it takes for an adenomatous (benign tumour) polyp to transform into carcinoma) in elderly US persons is dramatically increasing. Anyway, because the unknown duration over which the risk of CRC remains decreased following a normal colonoscopy, because colonoscopy in very elderly persons is associated with lower procedural completion rates and possibly higher complication rates, and in light that very elderly people have shorter life expectancies potentially limiting the benefits of screening procedures, decisions to undergo a colonoscopy should always be based on the exam impact on elderly people life expectancy. The aim of this paper is to review all the literature data about screening in the elderly to underline a good and uniform behaviour strategy in people P75 years old.
Screening Definition Screening is a public health service in which members of a defined population, who do not necessarily perceive they are at risk of, or are already affected by a disease or its complications, are asked a question or offered a test, to identify those individuals who are more likely to be helped than harmed by further tests or treatment to reduce the risk of a disease or its complications. Persons >70 years do not necessarily usually perceive they are at risk of CRC. Actually, in the last years, the incidence of this disease has increased, the mortality has improved especially for those cases which were not precociously treated and where the delay in diagnosis and cure was frequently with serious consequences on health.3,4 Since, persons in their 70s and even 80s have a reasonable life expectancy 10–12 years, nowadays, further efforts are becoming necessary to ensure that this part of the population is informed and has the opportunity to make a decision regarding prevention of this disease. A prior history of neoplasia also remained a strong risk factor for CRC development and should always be considered when deciding the need for screening at every age.5 Screening methods for CRC include testing for blood in the stools (faecal occult blood test, FOBT), flexible sigmoidoscopy, colonoscopy and barium enema.
Limitations Screening has important ethical differences from clinical practice as the health service is targeting apparently healthy people, offering to help individuals to make better informed choices about their health. However, there are risks involved and it is important that people have realistic expectations of what a screening programme can deliver. Whilst screening has the potential to save lives or improve quality of life through early diagnosis of serious conditions,
529
it is not a fool-proof process. Screening can reduce the risk of developing a condition or its complications but it cannot offer a guarantee of protection. In any screening programme, there is an irreducible minimum of false positive results (wrongly reported as having the condition) and false negative results (wrongly reported as not having the condition). The National Screening Committee is increasingly presenting screening as risk reduction to emphasise this point. For all these reasons and because screening has not to be considered a guarantee of protection, screening colonscopy in very elderly persons (aged > or = 80 years), even if FOBT positive, should be performed only after careful consideration of potential benefits (screening colonoscopy in very elderly persons results in only 15% of the expected gain in life expectancy achieved in younger persons), risks (because of mechanical bowel preparation and dehydration, electrolyte disturbances, conscious sedation and hypoxic complications), tolerance of eventual antineoplastic treatments and patient preferences.6 As a practical rule, ‘‘vulnerable’’ and ‘‘frail’’ persons, persons with difficulty in performing tests of physical performance such as to get up and go tests, and persons with moderate dementia or other geriatric syndromes, should not undergo cancer screening except for very special circumstances that increase their risk of developing cancer over the following 2–3 years.7 If a patient is not expected to live long because of extreme age or severe illness, it does not make much sense to schedule a colonoscopy (in order to prevent the possibility of a future cancer that would not affect the patient’s well-being within the next 5 years anyway).8 Differently, in all the other cases, even if elderly, the patient should be strictly evaluated.9 In a trial analysing all colonoscopies and sigmoidoscopies which were performed between January 1995 and December 2000 in patients older than 80 years (781 colonoscopies, 170 sigmoidoscopies; mean age 84.3 years) the most frequent observed indications were: abdominal pain (n = 144; 15%), bleeding (n = 115; 12%), constipation (n = 97; 10%), anaemia (n = 85; 9%) and history of polyps (n = 78; 8%). Colonoscopy was completed successfully to the coecum in 71%; 214 examinations were unremarkable (23%). Frequent pathologic findings were: diverticular disease (n = 396; 42%), polyps (n = 256; 27%) and colorectal carcinoma (n = 75; 8%). Curative surgery was possible in 55% and palliative surgery in 9% of patients with CRC, respectively. A complication was observed in six patients (0.6%), four bleedings following polypectomy, one perforation after dilatation of a stenotic tumour and one transient neurologic deficit. From the trial, endoscopy of the lower gastrointestinal tract appeared feasible in geriatric patients with a low rate of complications. The low number of normal findings and the frequent diagnosis of CRC were remarkable. In conclusion, in spite of old age more than half of the patients with carcinoma could be operated curatively emphasizing the importance of endoscopic investigations in this age group. Anyway, the suggestion, is to reserve endoscopies only to FOBT positive cases (as in younger population). Target population The age to begin CRC screening is based on the risk of neoplasia and is published in screening guidelines. The age to stop screening is unknown but should be based, in part, on the same principle. In the European Union (EU), current
530 recommendations endorse screening for all persons from 50 years to 74 years old, every one to two years. Actually, even though CRC screening is recommended, among patients with cancer, only a minority of them underwent a previous screening procedure (almost 94% of them had in fact never had a colonoscopy until the one that diagnosed their cancer). Screening is potentially a lifesaving procedure.10 It either prevents from getting cancer or if it does pick up cancer, it is at an earlier more curable stage. Investments in screening and polypectomy either in younger or in older persons decrease CRC-related costs, including screening and surveillance (cure rates for CRC are, in fact, high when the disease is detected and treated early).11 Recent trials on a big number of persons, confirm these results and report similar rates of neoplasia recurrence among patients of different gender and age groups on surveillance colonscopy.12 No decline in yield of advanced neoplasia is in fact observed to justify stopping screening colonscopy in the elderly.13 Nevertheless, whether or not screening will make a difference for an individual, depends not only on age but also to other existing illnesses (some older people may in fact experience more complications during screening tests increasing their risk) or potential life expectancy.8 Nowadays, the physician’s abilities to accurately estimate life expectancy for individual persons is often poor and, at present, even calculated estimations are of questionable validity. To compare and understand the effect of screening colonoscopy on the life expectancy of older and younger persons better, researchers conducted a study among persons in three age groups: 50–54, 75–79 and 80 or older.6 All persons underwent screening colonoscopy. None of the persons experienced complications from the procedure. Colorectal polyps were detected more frequently in older persons: polyps were detected by colonoscopy in 14% of persons between the ages of 50 and 54, 27% of persons between the ages of 75 and 79, and 29% of persons age 80 or older. In spite of the more frequent detection of polyps in older persons, the increase in life expectancy that resulted from colonoscopy was smaller for older persons than for younger persons. Among persons between the ages of 50 and 54, the average gain in life expectancy that resulted from screening colonoscopy was roughly 10 months. In contrast, among persons aged 80 or older, the average gain in life expectancy was roughly one-and-a-half months. Also in this case, the researchers concluded that screening colonoscopy in very elderly persons should be performed only after careful consideration of the potential benefits, risks and patient decisions. To assess the impact of informed consent on elderly persons’ CRC screening preferences or decisions a randomised controlled trial was also done.14 Three hundred and ninety nine elderly persons visiting their primary care provider for routine office visits were studied. Persons were randomised to receive either a scripted control message briefly describing CRC screening methods or one of two informational interventions simulating an informed consent presentation about CRC screening. One intervention described CRC mortality risk reduction in relative terms; the other, in absolute terms. The main outcome measure was intent to begin or continue FOBT, flexible sigmoidoscopy, or both. There was no difference in screening interest between the control group and the two information groups (p = 0.8).
L.M. Pasetto, S. Monfardini The majority (63%) of persons intended to begin or continue CRC screening. Informed persons were able to gauge more accurately the positive predictive value of screening (p = 0.0009). Control persons rated the efficacy of screening higher than persons receiving relative risk reduction information did, who rated it higher than persons receiving absolute risk reduction information (p = 0.0002). Elderly persons appeared to understand CRC screening information and use it to gauge the efficacy of screening, but provision of information had no impact on their preferences for screening. In view of the large proportion who preferred not to be screened, authors concluded that elderly persons should be involved in the screening decision. However, factors other than provision of information must determine their CRC screening preferences.
Clinical highlights Nowadays, CRC screening is recommended by UE for all persons 50–74 years of age (of any gender) using an annual FOBT (there is strong evidence to support that FOBT screening could reduce CRC mortality by 15% to 33% in a targeted population of 50–74 year olds).15–22 All positive tests should be followed up with colonoscopy.23 Flexible sigmoidoscopy and barium enema every 5 years, total colon evaluation every 10 years or faecal immunochemical test (FIT) can at present not be recommended for population screening; their effectiveness as a screening tool should be evaluated in randomised controlled trials. Among the various tests which have been used for screening, only the FOBT, to date, has been shown to be effective and evaluated in randomized trials as the initial screening test also in the elderly population. For its characteristics, it is in fact well appreciated by older population but, by itself and used alone, it carries negligible risk with false positive results so it could be associated to a sigmoidoscopy. Negative flexible sigmoidoscopy exam done between the ages of 76 and 79 make repeat exams after age 80 unnecessary. Colonoscopy (as has been the practice in most randomized trials), presents low but measurable risks of serious complications; in persons older than 74 years it should be reserved only for doubtful situations (i.e. positive FOBT) or for high risk persons.24
Conclusion Since, an estimated 90/100,000 inhabitants per year CRC deaths are expected to occur in patients older than 65 and since the majority of these would be aged 65 or older (65–78% CRC) we believe there could be a substantial potential for population benefit with CRC screening. Moreover, evaluating that 75 deaths and 611 perforations could result from diagnostic colonoscopy with a biennial screening program that is in contrast to an estimated reduction in CRC mortality of 16.7% (or 7740 deaths) with biennial screening over the same 10 years period, at the individual level, the lifetime probability of death from CRC would fall from 0.29% to 0.19% for an individual who participates in all screening events; the lifetime risk of colonoscopy-induced death would be 0.005% for that same individual.25 Clearly, these estimates are difficult to verify/quantify at the
Colorectal cancer screening in elderly patients: When should be more useful? population-level, as most studies reporting colonoscopy complications are carried out in patient groups that include symptomatic individuals. The risks among a healthy screening population are so low that they are difficult to estimate from the randomised trials presented to date. Nevertheless, while the benefits clearly outweigh the risks (an early detection of cancer may prevent the need of emergency surgery, whose mortality and morbidity increase with age),26 any individual contemplating screening with the FOBT should be made aware of both the risks and benefits prior to the initial screen. For a screening test to have a population-based impact, there must be adequate uptake (i.e. participation) in the target population (as the elderly one, i.e.) but any recommendations about population-based CRC screening may have resource implications. Resources may differ among provinces so provincial strategies may need to take this into account. Prime resource impacts include the costs of the initial medical consultation prior to taking the FOBT and the availability of resources for colonoscopy or other follow-up diagnostic tests, such as double contrast barium enema or flexible sigmoidoscopy for some geographic areas. In conclusion, in order to ensure quality screening which maximizes benefits and minimizes potential risks and costs, ideally screening should be within an organized and structured environment, with the following elements in place. First of all it should be clear, with concise and understandable information for persons and physicians on the risks and benefits of screening and on the administration of the test: that a colonoscopy in older than 80 years ‘‘vulnerable’’ or ‘‘frail’’ persons (even if FOBT positive) may be related to more risks than those reported in younger persons because of comorbidities and lower benefits because a precocious diagnosis in this category might not be necessarily linked to an adequate subsequent surgery or chemotherapy (for patient or relative refusal or opposition of the surgeon or oncologist due to the patient’s general health condition). Secondly, standardized protocols and procedures with a single entry test and options for follow-up should be organized: all persons older than 75 years might benefit of an annual FOBT; from 75 to 80 years, a flexible sigmoidoscopy may be only recommended after a positive FOBT for ‘‘frail’’ people (after 80 years the life expectancy might be a limit to the utility of the procedure); in the same five years, a colonoscopy may be recommended after any positive test in only ‘‘fit’’ elderly persons with the prospective of a possible future radical treatment. For all ‘‘frail’’ persons with the same age to which a radical treatment should be denied because of their general health, a cancer screening could be unsafe. Thirdly, systematic tracking and evaluation of all screening invitations (if used), testing frequency, results (including false positive and false negative rates), follow-up and outcomes should be recommended: a reduced number of elderly patient agreement should be an indication to sensitize them or their families towards the importance of the question. Resources for screening should be built up as appropriate. Recognizing disparity in human and financial resources, provinces may choose to phase in organized screening as resources permit. Recommendations, based on current evidence, should guarantee that screening is offered to a target population of elderly aged P75 years of age, with a good life expec-
531
tancy (>5 years), with a low risk of quality of life compromising even when it is unlikely to shorten the survival, ‘‘fit’’ or ‘‘vulnerable’’ with low grade comorbidities or with a moderate dementia or geriatric syndromes; these individuals might be screened at least every two years, recognizing that annual screening would have slight improvement in mortality reduction over biennial, but requires increased resources. The benefits of screening outweigh the risks and high quality population-based screening programs can reduce CRC mortality, specially in the high risk population (either because of first grade relatives affected by CRC or positive anamnesis for adenomas or chronic bowel inflammatory diseases or hereditary colic adenomatosis). Recognizing, however, that there are associated risks including death, the following elements need to be in place to protect the rights of elderly population and to maximize the benefits of screening: informed consent at the outset, including awareness of the risks and benefits of the entire screening cascade and not limited to the initial test; public awareness campaigns and promotional material including information on primary prevention and awareness of symptoms to inform the public of the availability of screening; a high priority on quality assurance and monitoring, including criteria for endoscopy, to minimize potential risks; active education of persons and physicians; ongoing evaluation procedures to ensure that organized screening continues only if appropriate participation rate and level of safety can be maintained in the Italian context.
References 1. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics 1999. Cancer J Clin 1999;49:8–31. 2. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J, editors. Cancer Incidence in Five Continents, vol. VII, IARC Scientific Publications No. 143, Lyon: IARC Press; 1997. 3. Jemal A, Clegg LX, Ward E, et al. Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer 2004;101(1):3–27. 4. Kemppainen M, Raiha I, Rahala T, Sourander L. Delay of diagnosis in colorectal cancer in the elderly. Age Ageing 1993;22(4):260–4. 5. Harewood GC, Lawlor GO, Larson MV. Incident rates of colonic neoplasia in older patients: When should we stop screening? J Gastroenterol Hepatol 2006;21(6):1021–5. 6. Lin OS, Kozarek RA, Schembre DB, et al. Screening colonoscopy in very elderly patients: Prevalence of neoplasia and estimated impact on life expectancy. JAMA 2006;295(20):2411–2. 7. Gill TM, Baker DI, Gottschalk M, et al. A program to prevent functional decline in physically frail elderly persons who live at home. N Engl J Med 2002;347:1068–70. 8. Ko CW, Sonnenberg A. Comparing risks and benefits of colorectal cancer screening in elderly patients. Gastroenterology 2005;129(4):1342–4. 9. Kirchgatterer A, Hubner D, Aschl G, Hinterreiter M, Stadler B, Knoflach P. Colonoscopy and sigmoidoscopy in patients aged eighty years or old. Z Gastroenterol 2002;40(12):951–6. 10. Cooper GS, Payes JD. Receipt of colorectal testing prior to colorectal carcinoma diagnosis. Cancer 2005;103(4):696–701. 11. Ladabaum U, Phillips KA. Colorectal cancer screening differential costs for younger versus older Americans. Am J Prev Med 2006;30(5):378–84. 12. Harewood GC, Lawlor GO. Incident rates of colonic neoplasia according to age and gender: Implications for surveillance
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L.M. Pasetto, S. Monfardini colonoscopy intervals. J Clin Gastroenterol 2005;39(10): 894–9. Stevens T, Burke CA. Colonoscopy screening in the elderly: when to stop? Am J Gastroenterol 2003;98(8):1881–5. Wolf AM, Schorling JB. Does informed consent alter elderly patients’ preferences for colorectal cancer screening? Results of a randomised trial. J Gen Int Med 2000;15(1):24–30. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota colon cancer control study. N Engl J Med 1993;328:672. Mandel JS, Church TR, Ederer F, et al. Colorectal cancer mortality: Effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst 1999;91:434–7. Hardcastle JD, Chamberlain JO, Robinson MHE, et al. Randomised controlled trial of faecal-occult blood screening for colorectal cancer. Lancet 1996;348:1472–7. Kronborg O, Fenger C, Olsen J, et al. Randomized study of screening for colorectal cancer with faecal occult blood test. Lancet 1996;348:1467–71. Kewenter J, Brevenge H, Engaras B, Haglind E, Ahren C. Results of screening, rescreening and follow-up in a prospective randomised study for detection of colorectal cancer by faecal occult blood testing. Results of 68,308 subjects. Scand J Gastroenterol 1994;29:468–73.
20. Tazi MA, Faivre J, Dassonville F, Lamour J, Milan C, Durand G. Participation in faecal occult blood screening for colorectal cancer in a well defined French population: Results of five screening rounds from 1988 to 1996. J Med Screening 1997;4:147–51. 21. Faivre J, Tazi MA, Milan C, Lejeune C, Durand G, Lamour J. Controlled trial of faecal occult blood screening for colorectal cancer in Burgundy (France). Results of the first 9 years. Gastroenterology 1999;116:A400., summary. 22. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2006. Ca Cancer J Clin 2006;56:11–25. 23. Recommendations on cancer screening in the European Union. Advisory Committee on Cancer Prevention. Eur J Cancer, 2000;36:1473–8. 24. Simon JB. Fecal occult blood testing: Clinical value and limitations. Gastroenterologist 1998;6:66–78. 25. Frazier AL, Colditz GA, Fuchs CS, et al. Cost-effectiveness of screening for colorectal cancer in the general population. JAMA 2000;284:1954–61. 26. Kemeny MM, Bush-Devearaux E, Merriam LT, et al. Cancer surgery in the elderly. Hematol/Oncol Clin N Am 2000;14: 169–92.
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/ctrv
CONTROVERSY
Colorectal cancer screening in elderly patients: When should be more useful? Lara Maria Pasetto *, Silvio Monfardini Istituto Oncologico Veneto, IRCCS: Medical Oncology 2nd, Via Gattamelata 64, 35128 Padova, Italy Received 21 February 2007; received in revised form 10 April 2007; accepted 15 April 2007
KEYWORDS Elderly; Screening; Colorectal cancer
Summary Current guidelines endorse colon cancer screening every 5–10 years in persons over 50 years of age. However, there is no consensus regarding what age is appropriate to stop screening. Prior history of neoplasia seems to be a strong risk factor for colorectal neoplasia development in elderly people and should be considered when deciding the need for continuing screening/surveillance, however, clinical judgment of comorbidities is still required to individualize screening practice. Screening colonoscopy in very elderly persons (aged P80 years), i.e. should be performed only after careful consideration of potential benefits, risks and patient preferences. The aims of this paper are to: (1) determine the best type of colorectal cancer screening (faecal occult blood testing, flexible sigmoidoscopy, double-contrast barium enema and colonoscopy) and its association with age and health status among elderly veterans and (2) describe the outcomes of colorectal cancer screening among older veterans who have widely differing life expectancies (based on age and health status). c 2007 Elsevier Ltd. All rights reserved.
Introduction
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer deaths in North America. The incidence, that is approximately 650,000 cases per year worldwide and 30,000 in Italy, has increased in recent years while the mortality, that was approximately of 278,446 male and 250,532 female cases per year worldwide in 2002 and 9061 male and 7909 female * Corresponding author. Tel.: +39 049 8215931; fax: +39 049 8215932. E-mail addresses: [email protected] (L.M. Pasetto), [email protected] (S. Monfardini).
cases in Italy in the same year, has decreased or stabilised.1 In persons over 85 years, CRC constitutes, one third of all neoplasms with 70% of patients aged 65 years or older.2 Particularly, in persons >65 years old, the incidence of colon cancer is about 120 new cases per 100,000 inhabitants per year (and in persons >75 years old is about 200/100,000 inhabitants per year) and mortality is about 90 per 100,000 inhabitants per year.3 The time from the first symptom to the first medical consultation in the elderly is so long and it is about 113.4 days (16.2 weeks) for rectal cancer and 88.9 days (12.7 weeks) for colonic cancer. The time from first examination to treatment is 154.0 days (22.0 weeks) for rectal cancer and 135.1 days (19.3 weeks) for colonic cancer.4 Because of the dimension and the gravity of the
0305-7372/$ - see front matter c 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.ctrv.2007.04.004
Colorectal cancer screening in elderly patients: When should be more useful? problem, current guidelines recommend CRC screening for all persons 50 years or older, properly to anticipate the time of diagnosis, but at this moment there is no specific age limit above which screening is not recommended. Probably for this reason, nowadays, the number of screening colonoscopies for CRC and its precursor lesions (based on the estimate of the time it takes for an adenomatous (benign tumour) polyp to transform into carcinoma) in elderly US persons is dramatically increasing. Anyway, because the unknown duration over which the risk of CRC remains decreased following a normal colonoscopy, because colonoscopy in very elderly persons is associated with lower procedural completion rates and possibly higher complication rates, and in light that very elderly people have shorter life expectancies potentially limiting the benefits of screening procedures, decisions to undergo a colonoscopy should always be based on the exam impact on elderly people life expectancy. The aim of this paper is to review all the literature data about screening in the elderly to underline a good and uniform behaviour strategy in people P75 years old.
Screening Definition Screening is a public health service in which members of a defined population, who do not necessarily perceive they are at risk of, or are already affected by a disease or its complications, are asked a question or offered a test, to identify those individuals who are more likely to be helped than harmed by further tests or treatment to reduce the risk of a disease or its complications. Persons >70 years do not necessarily usually perceive they are at risk of CRC. Actually, in the last years, the incidence of this disease has increased, the mortality has improved especially for those cases which were not precociously treated and where the delay in diagnosis and cure was frequently with serious consequences on health.3,4 Since, persons in their 70s and even 80s have a reasonable life expectancy 10–12 years, nowadays, further efforts are becoming necessary to ensure that this part of the population is informed and has the opportunity to make a decision regarding prevention of this disease. A prior history of neoplasia also remained a strong risk factor for CRC development and should always be considered when deciding the need for screening at every age.5 Screening methods for CRC include testing for blood in the stools (faecal occult blood test, FOBT), flexible sigmoidoscopy, colonoscopy and barium enema.
Limitations Screening has important ethical differences from clinical practice as the health service is targeting apparently healthy people, offering to help individuals to make better informed choices about their health. However, there are risks involved and it is important that people have realistic expectations of what a screening programme can deliver. Whilst screening has the potential to save lives or improve quality of life through early diagnosis of serious conditions,
529
it is not a fool-proof process. Screening can reduce the risk of developing a condition or its complications but it cannot offer a guarantee of protection. In any screening programme, there is an irreducible minimum of false positive results (wrongly reported as having the condition) and false negative results (wrongly reported as not having the condition). The National Screening Committee is increasingly presenting screening as risk reduction to emphasise this point. For all these reasons and because screening has not to be considered a guarantee of protection, screening colonscopy in very elderly persons (aged > or = 80 years), even if FOBT positive, should be performed only after careful consideration of potential benefits (screening colonoscopy in very elderly persons results in only 15% of the expected gain in life expectancy achieved in younger persons), risks (because of mechanical bowel preparation and dehydration, electrolyte disturbances, conscious sedation and hypoxic complications), tolerance of eventual antineoplastic treatments and patient preferences.6 As a practical rule, ‘‘vulnerable’’ and ‘‘frail’’ persons, persons with difficulty in performing tests of physical performance such as to get up and go tests, and persons with moderate dementia or other geriatric syndromes, should not undergo cancer screening except for very special circumstances that increase their risk of developing cancer over the following 2–3 years.7 If a patient is not expected to live long because of extreme age or severe illness, it does not make much sense to schedule a colonoscopy (in order to prevent the possibility of a future cancer that would not affect the patient’s well-being within the next 5 years anyway).8 Differently, in all the other cases, even if elderly, the patient should be strictly evaluated.9 In a trial analysing all colonoscopies and sigmoidoscopies which were performed between January 1995 and December 2000 in patients older than 80 years (781 colonoscopies, 170 sigmoidoscopies; mean age 84.3 years) the most frequent observed indications were: abdominal pain (n = 144; 15%), bleeding (n = 115; 12%), constipation (n = 97; 10%), anaemia (n = 85; 9%) and history of polyps (n = 78; 8%). Colonoscopy was completed successfully to the coecum in 71%; 214 examinations were unremarkable (23%). Frequent pathologic findings were: diverticular disease (n = 396; 42%), polyps (n = 256; 27%) and colorectal carcinoma (n = 75; 8%). Curative surgery was possible in 55% and palliative surgery in 9% of patients with CRC, respectively. A complication was observed in six patients (0.6%), four bleedings following polypectomy, one perforation after dilatation of a stenotic tumour and one transient neurologic deficit. From the trial, endoscopy of the lower gastrointestinal tract appeared feasible in geriatric patients with a low rate of complications. The low number of normal findings and the frequent diagnosis of CRC were remarkable. In conclusion, in spite of old age more than half of the patients with carcinoma could be operated curatively emphasizing the importance of endoscopic investigations in this age group. Anyway, the suggestion, is to reserve endoscopies only to FOBT positive cases (as in younger population). Target population The age to begin CRC screening is based on the risk of neoplasia and is published in screening guidelines. The age to stop screening is unknown but should be based, in part, on the same principle. In the European Union (EU), current
530 recommendations endorse screening for all persons from 50 years to 74 years old, every one to two years. Actually, even though CRC screening is recommended, among patients with cancer, only a minority of them underwent a previous screening procedure (almost 94% of them had in fact never had a colonoscopy until the one that diagnosed their cancer). Screening is potentially a lifesaving procedure.10 It either prevents from getting cancer or if it does pick up cancer, it is at an earlier more curable stage. Investments in screening and polypectomy either in younger or in older persons decrease CRC-related costs, including screening and surveillance (cure rates for CRC are, in fact, high when the disease is detected and treated early).11 Recent trials on a big number of persons, confirm these results and report similar rates of neoplasia recurrence among patients of different gender and age groups on surveillance colonscopy.12 No decline in yield of advanced neoplasia is in fact observed to justify stopping screening colonscopy in the elderly.13 Nevertheless, whether or not screening will make a difference for an individual, depends not only on age but also to other existing illnesses (some older people may in fact experience more complications during screening tests increasing their risk) or potential life expectancy.8 Nowadays, the physician’s abilities to accurately estimate life expectancy for individual persons is often poor and, at present, even calculated estimations are of questionable validity. To compare and understand the effect of screening colonoscopy on the life expectancy of older and younger persons better, researchers conducted a study among persons in three age groups: 50–54, 75–79 and 80 or older.6 All persons underwent screening colonoscopy. None of the persons experienced complications from the procedure. Colorectal polyps were detected more frequently in older persons: polyps were detected by colonoscopy in 14% of persons between the ages of 50 and 54, 27% of persons between the ages of 75 and 79, and 29% of persons age 80 or older. In spite of the more frequent detection of polyps in older persons, the increase in life expectancy that resulted from colonoscopy was smaller for older persons than for younger persons. Among persons between the ages of 50 and 54, the average gain in life expectancy that resulted from screening colonoscopy was roughly 10 months. In contrast, among persons aged 80 or older, the average gain in life expectancy was roughly one-and-a-half months. Also in this case, the researchers concluded that screening colonoscopy in very elderly persons should be performed only after careful consideration of the potential benefits, risks and patient decisions. To assess the impact of informed consent on elderly persons’ CRC screening preferences or decisions a randomised controlled trial was also done.14 Three hundred and ninety nine elderly persons visiting their primary care provider for routine office visits were studied. Persons were randomised to receive either a scripted control message briefly describing CRC screening methods or one of two informational interventions simulating an informed consent presentation about CRC screening. One intervention described CRC mortality risk reduction in relative terms; the other, in absolute terms. The main outcome measure was intent to begin or continue FOBT, flexible sigmoidoscopy, or both. There was no difference in screening interest between the control group and the two information groups (p = 0.8).
L.M. Pasetto, S. Monfardini The majority (63%) of persons intended to begin or continue CRC screening. Informed persons were able to gauge more accurately the positive predictive value of screening (p = 0.0009). Control persons rated the efficacy of screening higher than persons receiving relative risk reduction information did, who rated it higher than persons receiving absolute risk reduction information (p = 0.0002). Elderly persons appeared to understand CRC screening information and use it to gauge the efficacy of screening, but provision of information had no impact on their preferences for screening. In view of the large proportion who preferred not to be screened, authors concluded that elderly persons should be involved in the screening decision. However, factors other than provision of information must determine their CRC screening preferences.
Clinical highlights Nowadays, CRC screening is recommended by UE for all persons 50–74 years of age (of any gender) using an annual FOBT (there is strong evidence to support that FOBT screening could reduce CRC mortality by 15% to 33% in a targeted population of 50–74 year olds).15–22 All positive tests should be followed up with colonoscopy.23 Flexible sigmoidoscopy and barium enema every 5 years, total colon evaluation every 10 years or faecal immunochemical test (FIT) can at present not be recommended for population screening; their effectiveness as a screening tool should be evaluated in randomised controlled trials. Among the various tests which have been used for screening, only the FOBT, to date, has been shown to be effective and evaluated in randomized trials as the initial screening test also in the elderly population. For its characteristics, it is in fact well appreciated by older population but, by itself and used alone, it carries negligible risk with false positive results so it could be associated to a sigmoidoscopy. Negative flexible sigmoidoscopy exam done between the ages of 76 and 79 make repeat exams after age 80 unnecessary. Colonoscopy (as has been the practice in most randomized trials), presents low but measurable risks of serious complications; in persons older than 74 years it should be reserved only for doubtful situations (i.e. positive FOBT) or for high risk persons.24
Conclusion Since, an estimated 90/100,000 inhabitants per year CRC deaths are expected to occur in patients older than 65 and since the majority of these would be aged 65 or older (65–78% CRC) we believe there could be a substantial potential for population benefit with CRC screening. Moreover, evaluating that 75 deaths and 611 perforations could result from diagnostic colonoscopy with a biennial screening program that is in contrast to an estimated reduction in CRC mortality of 16.7% (or 7740 deaths) with biennial screening over the same 10 years period, at the individual level, the lifetime probability of death from CRC would fall from 0.29% to 0.19% for an individual who participates in all screening events; the lifetime risk of colonoscopy-induced death would be 0.005% for that same individual.25 Clearly, these estimates are difficult to verify/quantify at the
Colorectal cancer screening in elderly patients: When should be more useful? population-level, as most studies reporting colonoscopy complications are carried out in patient groups that include symptomatic individuals. The risks among a healthy screening population are so low that they are difficult to estimate from the randomised trials presented to date. Nevertheless, while the benefits clearly outweigh the risks (an early detection of cancer may prevent the need of emergency surgery, whose mortality and morbidity increase with age),26 any individual contemplating screening with the FOBT should be made aware of both the risks and benefits prior to the initial screen. For a screening test to have a population-based impact, there must be adequate uptake (i.e. participation) in the target population (as the elderly one, i.e.) but any recommendations about population-based CRC screening may have resource implications. Resources may differ among provinces so provincial strategies may need to take this into account. Prime resource impacts include the costs of the initial medical consultation prior to taking the FOBT and the availability of resources for colonoscopy or other follow-up diagnostic tests, such as double contrast barium enema or flexible sigmoidoscopy for some geographic areas. In conclusion, in order to ensure quality screening which maximizes benefits and minimizes potential risks and costs, ideally screening should be within an organized and structured environment, with the following elements in place. First of all it should be clear, with concise and understandable information for persons and physicians on the risks and benefits of screening and on the administration of the test: that a colonoscopy in older than 80 years ‘‘vulnerable’’ or ‘‘frail’’ persons (even if FOBT positive) may be related to more risks than those reported in younger persons because of comorbidities and lower benefits because a precocious diagnosis in this category might not be necessarily linked to an adequate subsequent surgery or chemotherapy (for patient or relative refusal or opposition of the surgeon or oncologist due to the patient’s general health condition). Secondly, standardized protocols and procedures with a single entry test and options for follow-up should be organized: all persons older than 75 years might benefit of an annual FOBT; from 75 to 80 years, a flexible sigmoidoscopy may be only recommended after a positive FOBT for ‘‘frail’’ people (after 80 years the life expectancy might be a limit to the utility of the procedure); in the same five years, a colonoscopy may be recommended after any positive test in only ‘‘fit’’ elderly persons with the prospective of a possible future radical treatment. For all ‘‘frail’’ persons with the same age to which a radical treatment should be denied because of their general health, a cancer screening could be unsafe. Thirdly, systematic tracking and evaluation of all screening invitations (if used), testing frequency, results (including false positive and false negative rates), follow-up and outcomes should be recommended: a reduced number of elderly patient agreement should be an indication to sensitize them or their families towards the importance of the question. Resources for screening should be built up as appropriate. Recognizing disparity in human and financial resources, provinces may choose to phase in organized screening as resources permit. Recommendations, based on current evidence, should guarantee that screening is offered to a target population of elderly aged P75 years of age, with a good life expec-
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tancy (>5 years), with a low risk of quality of life compromising even when it is unlikely to shorten the survival, ‘‘fit’’ or ‘‘vulnerable’’ with low grade comorbidities or with a moderate dementia or geriatric syndromes; these individuals might be screened at least every two years, recognizing that annual screening would have slight improvement in mortality reduction over biennial, but requires increased resources. The benefits of screening outweigh the risks and high quality population-based screening programs can reduce CRC mortality, specially in the high risk population (either because of first grade relatives affected by CRC or positive anamnesis for adenomas or chronic bowel inflammatory diseases or hereditary colic adenomatosis). Recognizing, however, that there are associated risks including death, the following elements need to be in place to protect the rights of elderly population and to maximize the benefits of screening: informed consent at the outset, including awareness of the risks and benefits of the entire screening cascade and not limited to the initial test; public awareness campaigns and promotional material including information on primary prevention and awareness of symptoms to inform the public of the availability of screening; a high priority on quality assurance and monitoring, including criteria for endoscopy, to minimize potential risks; active education of persons and physicians; ongoing evaluation procedures to ensure that organized screening continues only if appropriate participation rate and level of safety can be maintained in the Italian context.
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