Recommendations on population screening for colorectal cancer in New Zealand. Members of the National Health Committee Working Party on Population Screening for Colorectal Cancer

The National Advisory Committee on Health and Disability invited a working party to make recommendations on population screening for colorectal cancer in New Zealand. Recent results from randomised controlled trials of screening with guaiac faecal occult blood tests have provided evidence that population screening could reduce mortality from colorectal cancer. However, given the modest potential level of benefit, the considerable commitment of health sector resources, and the small but real potential for harm, the working party does not recommend population screening for colorectal cancer with faecal occult blood tests in New Zealand. The working party does nto recommend pilot colorectal cancer screening programmes in New Zealand because pilot programmes cannot address the issues of concern: the modest potential benefit and the small, but real, potential for harm. The working party does not recommend faecal occult blood testing as a screening test for colorectal cancer in average-risk individuals outside a population screening programme. Those requesting screening by faecal occult blood test should be given information about the potential risks and benefits. Follow-up bowel investigations in the public health system cannot be guaranteed without an increased allocation of resources. As there is yet no evidence from randomised controlled trials that screening with flexible sigmoidoscopy, colonoscopy or double-contrast barium enema produces a reduction in colorectal cancer mortality, the working party does not recommend population screening with these modalities. Wider consultation and further consideration should be undertaken to develop appropriate advice on surveillance recommendations for groups identified to be at increased risk of colorectal cancer. These decisions should be reviewed as evidence of benefit from new types of faecal occult blood test and other screening modalities becomes available. The working party recognises that colorectal cancer is an important cause of morbidity and mortality and recommends that New Zealand participate in international research in this area.     

Screening, prevention and socioeconomic costs associated with the treatment of colorectal cancer

Colorectal cancer (CRC), the third most prevalent cancer worldwide, imposes a significant economic and humanistic burden on patients and society. One study conservatively estimated the annual expenditures for colorectal cancer to be approximately dollars US 5.3 billion in 2000, including both direct and indirect costs. However, other investigators estimated inpatient costs alone incurred in the US in 1994 to be around dollars US 5.14 billion. Therefore, the economic burden of colorectal cancer in the US could be projected to be somewhere in the range of dollars US 5.5-6.5 billion by considering that inpatient costs approximate 80% of total direct costs. No worldwide data have been published, but assuming that the US represents 25-40% of total expenditures in oncology, as seen for breast and lung cancers, a rough estimate for colorectal cancer would be in the range of dollars US 14-22 billion. Screening helps increase patient survival by diagnosing colorectal cancer early. The ideal method among the four tests most used (faecal occult blood test, flexible sigmoidoscopy, colonoscopy and double contrast barium enema) has not been identified. Economic studies of colorectal cancer screening are complex because of the many variables involved, as well as the fact that the outcomes must be followed for many years, and the lack of consensus on screening guidelines. Intuitively, modelling colorectal cancer is one way to overcome these hurdles; published modelling studies predict colorectal cancer screening programs to be within the threshold of dollars US 40000 per life-year saved. The faecal occult blood test appears to be the only clearly effective test, both from a clinical and an economic viewpoint. Important limitations are the invasiveness and inconvenience of the screening procedures, except faecal occult blood test. Patients' comfort and satisfaction are essential in improving compliance with screening recommendations, which appears to be low even in the US (35% of the general population aged over 40 years and 60% of the high-risk population), the country with the highest awareness and compliance in the world. Since colorectal cancer is generally a disease of the elderly, its economic burden is expected to grow in the near future, mainly due to population aging. Potential avenues to pursue in order to contain or reduce the economic burden of colorectal cancer would be the design and implementation of efficient screening programmes, the improvement of patient awareness and compliance with screening guidelines, the development of appropriate prevention programs (i.e. primary and secondary), and earlier diagnosis.     

Review article: Population screening for colorectal cancer

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.     

A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population

BACKGROUND: Colorectal cancer screening by guaiac faecal occult blood test has been shown to reduce the incidence and mortality of colorectal cancer in Western populations. The optimal faecal occult blood test, whether guaiac or immunochemical, for colorectal cancer screening in the Chinese population remains to be defined. AIM: To compare the performance characteristics of a sensitive guaiac-based faecal occult blood test (Hemoccult SENSA) and an immunochemical faecal occult blood test (FlexSure OBT) in a Chinese population referred for colonoscopy. METHODS: One hundred and thirty-five consecutive patients who were referred for colonoscopy and who met the study inclusion criteria took samples for the two faecal occult blood tests simultaneously from three successive stool specimens, with no dietary restrictions. All tests were developed and interpreted by a single experienced technician who was blind to the clinical diagnosis. The sensitivity, specificity and positive predictive value for the detection of colorectal adenomas and cancers were estimated for the two tests. RESULTS: The sensitivity, specificity and positive predictive value for the detection of significant colorectal neoplasia (adenomas > or = 1.0 cm and cancers) were 91%, 70% and 18% for Hemoccult SENSA and 82%, 94% and 47% for FlexSure OBT. The specificity and positive predictive value were significantly higher for FlexSure OBT than for Hemoccult SENSA (P < 0.001 and P = 0.016, respectively). Combining the positive results from both faecal occult blood tests did not improve the accuracy. CONCLUSION: The positive predictive value of the immunochemical faecal occult blood test for the detection of significant colorectal neoplasia was 29% better than that of the sensitive guaiac-based test. This may relate to the Chinese diet and requires further study. The poor specificity of the sensitive guaiac-based test, without dietary restriction, makes it less useful for colorectal cancer screening in a Chinese population.     

Review article: faecal occult blood testing for colorectal cancer

Major health organizations recommend colorectal cancer screening using faecal occult blood tests, sigmoidoscopy or both for patients 50 years of age or older who are at average risk for colorectal cancer. However, no specific recommendations have been made regarding choice of test from among the tests currently or soon to be available. Therefore, to aid clinicians in rationally choosing a particular test for faecal occult blood, published data are reviewed regarding the performance characteristics, strengths and weaknesses of the various faecal occult blood tests. New studies suggest that immunochemical tests (e.g. HemeSelect) or a combination of sensitive guaiac tests and immunochemical tests (e.g. Hemoccult Sensa and HemeSelect) are the most sensitive, specific tests for detecting colorectal carcinoma and colorectal polyps ≥ 1 cm.     

Should we be screening for colorectal cancer?

Mass population screening for asymptomatic neoplastic disease is now national policy in the UK for breast cancer and has been established for many years in the early diagnosis of carcinoma of the cervix. Cancer screening is based on the concept that treatment is more effective when the disease is localised and aims to detect it when it is at a less advanced clinico-pathological stage prior to the development of symptoms. Because colorectal cancer develops in benign adenomatous polyps which are often amenable to endoscopic resection, screening may both reduce the incidence of the disease as well as improving outcome from it. Flexible sigmoidoscopy screening focuses mainly on the detection of potentially malignant adenomas, their endoscopic removal producing a decrease in colorectal cancer incidence. It is a promising approach but conclusive data on effectiveness from a Medical Research Council-sponsored multicentre randomised controlled trial will not be available before 2006. Faecal occult blood testing aims to preferentially detect early stage invasive disease. Three randomised controlled trials of faecal occult blood screening show that the disease can be detected earlier in its development leading to reduced mortality from the disease--and that this is achieved at reasonable cost. The Department of Health is currently giving consideration to its national implementation.     

Can quantification of faecal occult blood predetermine the need for colonoscopy in patients at risk for non‐syndromic familial colorectal cancer?

BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial colorectal neoplasia undergo colonoscopic surveillance at intervals determined by clinically ascertained protocols. The quantitative immunochemical faecal occult blood test for human haemoglobin is specific and sensitive for significant colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine immunochemical faecal occult blood test efficacy for identifying significant neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We retrospectively identified consecutive at-risk patients who provided three immunochemical faecal occult blood tests before colonoscopy. Quantitative haemoglobin analysis was performed by the OC-MICRO automated instrument using the 100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non-advanced adenoma. The immunochemical faecal occult blood test was positive in 31 patients (12.3%). Sensitivity, specificity, positive and negative predictive values for cancer were: 100%, 90%, 16% and 100%, and for all significant neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal cancers and 74% of all significant neoplasia would have been identified by this one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A sensitive, non-invasive, interval screening test might be useful to predetermine the need for colonoscopy in this at-risk population and minimize unnecessary examinations. This favourable retrospective evaluation will be extended to a prospective study.     

As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia

Background Colorectal cancer screening and treatment are rapidly evolving. Aims To reappraise stool‐based colorectal cancer screening in light of changing test performance characteristics, lower test cost and increasing colorectal cancer care costs. Methods Using a Markov model, we compared faecal DNA testing every 3 years, annual faecal occult blood testing or immunochemical testing, and colonoscopy every 10 years. Results In the base case, faecal occult blood testing and faecal immunochemical testing gained life‐years/person and cost less than no screening. Faecal DNA testing version 1.1 at $300 (the current PreGen Plus test) gained 5323 life‐years/100 000 persons at $16 900/life‐year gained and faecal DNA testing version 2 (enhanced test) gained 5795 life‐years/100 000 persons at $15 700/life‐year gained vs. no screening. In the base case and most sensitivity analyses, faecal occult blood testing and faecal immunochemical testing were preferred to faecal DNA testing. Faecal DNA testing version 2 cost $100 000/life‐year gained vs. faecal immunochemical testing when per‐cycle adherence with faecal immunochemical testing was 22%. Faecal immunochemical testing with excellent adherence was superior to colonoscopy every 10 years. Conclusions As novel biological therapies increase colorectal cancer treatment costs, faecal occult blood testing and faecal immunochemical testing could become cost‐saving. The cost‐effectiveness of faecal DNA testing compared with no screening has improved, but faecal occult blood testing and faecal immunochemical testing are preferred to faecal DNA testing when patient adherence is high. Faecal immunochemical testing may be comparable to colonoscopy every 10 years in persons adhering to yearly testing.     

康健社区2012年大肠病变筛查结果分析

目的：调查社区居民大肠病变早发状况,评估筛查方案。方法：对社区健康档案数据库中40～70岁的常住人群采用问卷调查和免疫法粪便潜血试验相结合的方法进行初筛,应用全结肠镜进行精筛。结果：筛查1011人,高危人群为363人,高危阳性率35．90％。高危人群中有156人接受全结肠镜检查,高危人群受检率为42．98％。检出大肠病变（大肠癌、息肉）87例,其中早期癌1例,大肠癌检出率为98．91／10^5。结论：单项应用诊断早期大肠癌的正确率低。问卷调查和大便隐血试验对大肠癌诊断有一定价值,适合在社区普查。     

Influence of non-steroidal anti-inflammatory drugs on the outcome of faecal occult blood tests in screening for colorectal cancer.

Non-steroidal anti-inflammatory drugs have been accused of causing false positive results in faecal occult blood tests for colorectal cancer. A study was therefore performed in 10,931 people undergoing faecal occult blood screening tests to assess the effect of these drugs on the predictive value of a positive test result. Those with a positive result were interviewed and a full drug history was taken before they underwent a full colorectal examination. Of the 455 people with a positive result, 50 were taking non-steroidal anti-inflammatory drugs: 10 (20%) had colonic neoplasia. Of the 405 who were not taking non-steroidal anti-inflammatory drugs, 129 (32%) had colonic neoplasia. These detection rates were not significantly different, and the predictive value of a positive result for an adenoma larger than 1 cm was 14% in the group not taking anti-inflammatory drugs and 26% in the group taking them (not significant). These results suggest that a finding of occult faecal blood cannot be attributed to upper gastrointestinal tract bleeding caused by non-steroidal anti-inflammatory drugs and should be followed by a thorough colorectal examination.     

国内外大肠癌筛查现状及无创筛查方法进展

摘要： 大肠癌是严重威胁人类健康的恶性肿瘤之一, 其全球发病率和死亡率分居第3位和第2位。开展大肠癌筛查工作对大肠癌早发现、 早治疗具有重要意义。德国等经济发达国家上世纪七十年代就开始大肠癌筛查以降低其发生率和死亡率。我国也于1977年在部分大肠癌高发地区开展筛查工作, 近年在天津、 上海等大城市也开展了大肠癌筛查工作。笔者对国际和国内大肠癌筛查的现状进行综述, 探讨大肠癌筛查工作对降低大肠癌发病率和死亡率的意义, 并总结大肠癌筛查方法对筛查工作的影响。通过分析, 笔者认为国家健康计划、 科普宣传、 医保覆盖、 有效的监督机制以及合适的筛查方法是影响大肠癌筛查工作开展的重要因素。     

The investigation of colorectal disorders.

The investigation of colorectal disorders follows from a thorough clinical examination, examination of stools, and proctosigmoidoscopy. In many patients, barium enema examination will also be required, and the value of good air contrast examinations is stressed. Colonoscopy has revolutionised the diagnostic and therapeutic capabilities in colonic disease, but this examination is not readily available to all, its indications limited, and the risks and discomfort associated with it by no means small. In New Zealand, colorectal cancer is as common as anywhere else in the world, and the major hope of any improvement in this area is with preclinical diagnosis. This could be achieved by more widespread faecal occult blood testing especially in high risk groups (Table 2) and thorough investigation of those with positive results. Serological tests for colorectal cancer (carcino-embryonic antigen) have proved disappointing, and much less specific than originally hoped.     

小昆山社区结直肠癌筛查结果分析

目的：进行小昆山镇高危年龄段结直肠癌筛查,了解顺应率、发病率。方法：以全国大肠癌早诊早治项目规定的大肠癌筛查技术方案为依据,对45～74岁户籍居民进行结直肠癌筛查。以危险因素数量化评估问卷调查及大便隐血试验作为初筛,阳性者复筛行结肠镜检查。结果：应筛查12694人,实际参加筛查9167人,初筛顺应率为72.2%,阳性人数2234人;复筛人数571人,复筛顺应率为25.6%。发现结直肠癌10例,结直肠息肉及腺瘤190例,肠炎25例,其它2例。结论：结直肠癌筛查方案能够有效的从无症状人群中发现早期结直肠癌和癌前病变;小昆山地区结直肠癌筛查顺应性高于其它城市社区。     

A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test

BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically-developed, quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal test diagnostic efficacy and costs for identifying significant neoplasia. METHODS: Colonoscopies were performed on patients who prepared three daily guaiac faecal occult blood tests with or without immunochemical faecal tests. RESULTS: Total colonoscopy was performed on 151 subjects who prepared both guaiac and immunochemical faecal tests (group 1) and the positive predictive values (PPV) were also compared to those of 162 subjects undergoing colonoscopy for positive guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity, specificity, and PPVs for significant neoplasia with guaiac faecal occult blood test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy examinations needed to detect a significant neoplasm because of positive faecal occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An immunochemical faecal test maintains the high sensitivity of guaiac faecal occult blood test, but significantly reduces the colonoscopy burden and screening costs.     

Prevention and management of colorectal cancer in women

OBJECTIVE: To review prevention and management strategies for colorectal cancer, with an emphasis on studies pertaining to women. DATA SOURCES: Articles published from January 1990 through February 2001 identified through a MEDLINE search using the term colorectal cancer and the additional terms screening, prevention, and treatment. Additional references were identified from the bibliographies of the retrieved articles. DATA SYNTHESIS: Colorectal cancer is the third most common non-skin cancer in women, after breast and lung cancers. Many women underestimate their risk of colorectal cancer, which may lead them to underuse screening measures that have been proven to reduce disease morbidity and mortality. For average-risk women and men > or = 50 years of age, pharmacists should recommend regular screening for early detection and prevention of colorectal cancer. In its earliest, most curable stages, colorectal cancer is often asymptomatic. However, patients who report signs and symptoms, such as blood in the stool, abdominal pain, changes in bowel habits, unexplained weight loss, or iron deficiency anemia, should be referred for medical evaluation. The use of chemopreventive agents for colorectal cancer, such as nonsteroidal anti-inflammatory drugs, hormone replacement therapy, and dietary calcium, holds significant promise, but further studies are needed before these agents can be recommended for cancer prevention in the general population. Surgical resection is the primary treatment modality for colorectal cancer, and adjuvant chemotherapy is recommended in patients with stage III disease and some high-risk patients with stage II disease. Pharmacists should be aware that women are more susceptible to dose-related toxicity effects of fluorouracil and leucovorin combination chemotherapy, the first-line regimen for adjuvant chemotherapy. CONCLUSION: Although often perceived as a disease that primarily affects men, colorectal cancer is an equally important health concern for women. By providing education and counseling, pharmacists can help raise women's awareness of this disease and encourage them to take steps to significantly reduce their risk.     

郑州市某社区居民对大肠癌筛查的看法及认知情况的调查研究

目的 调查郑州市某社区居民对大肠癌筛查的看法及认知情况.方法 以郑州市某社区居民为对象进行调查,了解其对大肠癌筛查看法、不愿意进行筛查原因、疾病认知情况等.结果 对242户居民发放问卷并全部回收,均认为大肠癌筛查项目非常重要.但44户(18.2％)居民拒绝进行筛查,参与筛查居民有17名(7.0％)大便隐血试验阳性,有7名(41.2％)拒绝进一步行肠镜检查.认知方面,88.4％(214/242)不了解大肠癌高发病率与病死率现状;85.9％(208/242)不明确大肠癌危险因素;仅9.9％(24/242)会对大肠癌危险因素进行规避.结论 郑州市某社区居民对大肠癌认知度较低,虽认为大肠癌筛查的开展必要,但受时间等因素影响筛查率低,可通过一定干预措施提高大肠癌筛查率,以防控大肠癌.     

Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed

Background  Faecal occult blood tests (FOBT) are faulted by low sensitivity for advanced adenomatous polyps (AAP). Quantified, immunochemical, haemoglobin (Hb)-specific immunochemical FOBT (I-FOBT) measurements are now used for colorectal screening.
Aims  To correlate adenoma characteristics to amount of faecal Hb lost and to evaluate sensitivity and specificity for AAP by faecal Hb development threshold used and number of I-FOBTs collected.
Methods  Three daily I-FOBTs were collected and analysed in 1221 patients scheduled for colonoscopy. Faecal Hb was analysed as ngHb/mL of buffer and the highest result related to colonoscopy findings.
Results  In 1204 patients without cancer, colonoscopy identified adenomas in 294, 99 with AAPs. Adenoma patients had elevated faecal Hb increasing with advanced histology, size, pedunculated shape and multiplicity ( P < 0.001 for all). At 50 ngHb/mL threshold, sensitivity and specificity for AAPs were 54.5% (95%CI 44.7, 64.7) and 88.1% (95%CI 86.2, 90.1) for three tests. At higher thresholds, sensitivity decreased, but was significantly higher with more samples collected. Conversely, specificity increased at higher thresholds, but decreased with more samples.
Conclusions  Faecal Hb loss from adenomas is significantly associated with size, number and advanced features. Sensitivity and specificity for AAPs are determined by test threshold chosen and number of samples collected; these determine the number of colonoscopies needed for positive tests.     

Population screening for colorectal cancer

Each year in the UK, around 16,000 people die from colorectal cancer. At disease presentation, around 55% of people have advanced cancer that has spread to lymph nodes, metastasised to other organs or is so locally advanced that surgery is unlikely to be curative (Dukes' stage C or D). Overall 5-year survival for colorectal cancer in the UK is around 47-51% (compared to 64% in the USA), but only 7% at most in those presenting with metastatic disease. These facts underlie the current introduction of national bowel screening programmes in the UK. Here we assess the role of screening of the general population in reducing mortality from colorectal cancer. We do not consider the screening arrangements needed for high-risk populations, including those with inflammatory bowel disease or a strong family history of colorectal cancer.     

The evolution to stool DNA testing for colorectal cancer

Despite a variety of screening strategies and recent trends showing death rate stabilization, colorectal cancer still remains the second leading cause of overall cancer death. Current screening tools suffer from performance limitations, low patient acceptability, and marginal reliable access within the health care system. Noninvasive strategies present the lowest risk with the highest potential for patient satisfaction. However, serious implementation barriers exist requiring consistent programmatic screening, strict patient adherence, and poor sensitivity for adenomas. Colonoscopy remains an invasive screening test with the best sensitivity and specificity, but faces large financial costs, manpower requirements, patient access and adherence. Development of advanced molecular techniques identifying altered DNA markers in exfoliated colonocytes signify early or precancerous growth. Stool-based DNA testing provides an entirely noninvasive population-based screening strategy which patients can perform easier than faecal occult blood testing (FOBT). Large-scale prospective randomized control trials currently pending should help characterize accurate test performance, screening intervals, cost-effectiveness, direct comparison to FOBT and analysis of patient adherence. As tumour development pathways and potential target genes are further elucidated, refinements in multi-assay stool-based DNA testing portend enhanced test characteristics to detect and treat this genetically heterogeneous disease.     

上海市某社区全科门诊患者结直肠癌筛查意愿及参与行为调查

目的：了解社区居民参加结直肠癌筛查的意愿和行为,分析影响人群参与结直肠癌筛查的相关因素。方法：对2014年9月至10月前来社区卫生服务中心全科门诊就诊的患者进行问卷调查。结果：接受问卷调查的496位门诊患者中,170位参与了结直肠癌筛查,参与率为34.3%;参加筛查的前三位原因是：全科医生建议（43.3%）、检查免费（32.7%）、有助于早期发现结直肠癌（21.6%）;未参加筛查的前三位原因是：自己患癌症的可能性小（34.3%）、没时间（27.1%）、觉得意义不大（19.1%）;筛查参与意愿与年龄（P=0.033）和目前的工作状态（P=0.046）相关。结论：目前社区居民参与结直肠癌筛查的百分比偏低,全科医生要加强结直肠癌相关知识的宣教,提高居民对结直肠癌筛查工作的重视和参与度。