Colorectal cancer screening
Colorectal cancer screening
复制标题
DOI：
10.1002/bjs.9599
复制
发表时间：
2014-10
影响因子：
9.6
通讯作者：
R. Steele
中科院分区：
文献类型：
--
作者：
R. Steele
结直肠癌的人群筛查现已在英国所有组成国家展开。虽然不同国家的算法略有不同，但一线筛查试验是一种基于愈创木酚的粪便潜血试验(GFOBt)，其分析特征与随机临床试验(RCT)中使用的相同，后者证明了令人信服的疾病特异性死亡率下降1。最近的一项配对队列研究表明，目前的方案正在产生预期程度的死亡率下降2，尽管基于愈创木酚的测试存在重大缺陷。筛查的总体接受率仍然顽固地低于60%1。间歇性癌症(在检测结果为阴性后2年内出现的癌症)正日益得到承认，最近的数据表明，间歇性疾病约占筛查人群中诊断出的癌症的50%。最后一个不利因素是，目前的方案在预防结直肠癌方面缺乏效力；以英国使用的分析灵敏度计算，gFOBt不能确定足够数量的腺瘤以产生可衡量的预防效果4。尽管英国的这些筛查计划无疑在预防结直肠癌死亡，但未来的发展必须解决这些不足。一种方法是转向血液的定量粪便免疫化学检测(QFIT)。这具有专用于血红蛋白并提供粪便中血红蛋白浓度的值的优点。支持使用QFIT的最好证据来自荷兰的一项随机研究，5比较了QFIT在缓冲液中每毫升粪便中100纳克血红蛋白的截止值与基于愈创木酚的测试，后者的分析检测下限约为每毫升粪便400纳克血红蛋白。这项研究表明，QFIT有更好的摄取率，对癌症和腺瘤的检测具有更高的灵敏度，所需的数量与结肠镜相似。然而，这是以较高的阳性率为代价的，因此需要更多的结肠镜检查。如果以与标准gFOBt相同的分析灵敏度使用QFIT，则两种检测在疾病检测方面的执行方式基本相同。为了减少间歇性癌变率和增加腺瘤的发现机会，似乎有必要降低分析阈值，以降低阳性预测值，增加所需的结肠镜检查次数。考虑到英国内窥镜服务的压力，这目前是令人不快的，但越来越多的证据表明，使用QFIT对有症状的患者进行分类可以极大地减少有症状人群所需的结肠镜检查数量，并释放用于筛查的资源6。此外，应该有可能以更智能的方式使用QFIT的量化力量。例如，众所周知，间歇性癌症在女性中比男性更常见，而且女性粪便中的血液浓度明显低于男性。因此，应该有可能通过使用不同的截断点来触发结肠镜检查来解决女性间歇性癌症的问题。降低分析阈值和增加筛查之间的间隔也是可行的，从而可以在结肠镜检查资源方面以成本中立的方式提高测试的灵敏度。再多一点想象力，也有可能根据粪便血红蛋白浓度指标改变筛查间隔，因为众所周知，这与罹患重大肿瘤疾病的风险成正比。因此，粪便中血红蛋白浓度接近预定界限的个体可能会在6个月内进行重复检测，而无法检测到血红蛋白的个体可能会将下一次检测推迟几年。对粪便血红蛋白水平随时间的变化知之甚少，如果我们要优化基于粪便血红蛋白检测的筛查，就需要注意这一点。当然，随机对照试验有很好的证据表明，使用柔性乙状结肠镜作为主要筛查试验可以降低结直肠癌的死亡率和发病率。这项测试在英格兰55岁左右推出，但不是在苏格兰，那里的FOBT筛查开始年龄是50岁，而在英格兰是60岁。一项初步研究
Population screening for colorectal cancer has now been rolled out across all the constituent countries of the UK. Although the algorithms differ slightly from one country to another, the first-line screening test is a guaiac-based faecal occult blood test (gFOBT) with the same analytical characteristics as those used in the randomized clinical trials (RCTs) that demonstrated convincing reductions in disease-specific mortality1. A recent matched cohort study has indicated that the current programme is producing a mortality reduction of the expected magnitude2, even though the guaiac-based test has significant weaknesses. The overall uptake of screening remains stubbornly below 60 per cent1. Interval cancers (those arising within 2 years of a negative test result) are being increasingly recognized, with recent data suggesting that interval disease accounts for approximately 50 per cent of the cancers diagnosed in the screened population3. A final disadvantage relates to the lack of efficacy of the current programme in the prevention of colorectal cancer; gFOBT at the analytical sensitivity used in the UK does not identify sufficient numbers of adenomas to have a measurable preventive effect4. Although these UK screening programmes are undoubtedly preventing colorectal cancer deaths, future developments must address these deficiencies. One approach is to move to quantitative faecal immunochemical testing (QFIT) for blood. This has the advantages of being specific for haemoglobin and providing a value for the concentration of haemoglobin in the stool. The best evidence supporting the use of QFIT comes from a randomized study5 in the Netherlands comparing QFIT at a cut-off of 100 ng haemoglobin per ml faeces in buffer with a guaiac-based test that has an analytical detection limit of around 400 ng haemoglobin per ml faeces. This study demonstrated better uptake with QFIT, and a higher sensitivity for both cancer and adenoma detection with a similar number needed to colonoscope. However, this came at the expense of a higher positivity rate and therefore the need for a larger overall number of colonoscopies. If QFIT is used at the same analytical sensitivity as the standard gFOBT, both tests perform in much the same way in terms of disease detection. For QFIT to reduce the interval cancer rate and increase the chances of adenoma detection it seems that it would be necessary to reduce the analytical threshold such that the positive predictive value would decrease and the number of colonoscopies required would increase. This is currently unpalatable given the pressures on endoscopy services in the UK, but there is increasing evidence that using QFIT to triage symptomatic patients could dramatically reduce the number of colonoscopies required in the symptomatic population and free up resources for screening6. Furthermore, it should be possible to use the quantitative power of QFIT in a more intelligent way. For example, it is known that interval cancers are more common in women than in men, and that the concentration of blood in stool is significantly lower in women than in men7. It should therefore be possible to address the problem of interval cancers in women by using a differential cut-off to trigger colonoscopy. It is also feasible to decrease the analytical threshold and increase the interval between screens so that sensitivity of the test may be improved in a cost-neutral manner in terms of colonoscopy resource. With a little more imagination it may also be possible to vary the interval between screens based on the index faecal haemoglobin concentration, as it is known that this is directly proportional to the risk of having significant neoplastic disease8. Thus an individual with a faecal haemoglobin concentration close to a predetermined cut-off may have a repeat test within 6 months, whereas someone with undetectable haemoglobin may have their next test deferred for a few years. Little is known about variations in faecal haemoglobin levels with time and this requires attention if we are to optimize screening based on faecal haemoglobin detection. Of course, there is good evidence from RCTs that using flexible sigmoidoscopy as the primary screening test can reduce both the mortality from, and incidence of, colorectal cancer9. This test is being rolled out at around the age of 55 years across England, but not in Scotland where FOBT screening starts at age 50 years as opposed to 60 years in England. A pilot study of