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Proposals for lung cancer screening in the UK

Proposals for lung cancer screening in the UK Cancer Imaging (2001) 2, 6–16 Multidisciplinary Symposium — Screening for Cancer Monday 15 October 2001, 10.20–12.45 Janet E Husband Academic Department of Diagnostic Radiology, The Royal Marsden NHS Trust, Downs Road, Sutton, Surrey SM2 5PT, UK Lung cancer is the most frequent cause of cancer death in The National Cancer Institute is reassessing the role the Western world. Low dose Spiral CT offers a new of chest radiography in a large randomized controlled approach to lung cancer detection and early results from trial, the Prostate–Lung–Colorectal–Ovarian (PLCO) screening studies are promising. United Kingdom proposals Trial, which is designed to have sufficient statistical for a randomized controlled trial of lung cancer screening power to identify a reduction in lung cancer mortality of [10] of spiral CT vs. a control arm of no screening is discussed. 10% . While chest radiography may identify lung lesions greater than 1 cm in diameter, Spiral CT can identify pulmonary nodules less than 5 mm in diameter. This has opened the way for the use of Spiral CT in early Introduction detection of peripheral lung cancers. Lung cancer is now the leading cause of cancer death in Early results from non-randomized trials in Japan the Western world and accounts for more deaths than and the United States using Spiral CT for screening lung the total from colon, lung and prostate cancer combined cancer have shown that approximately four times as [1] in the United States . Although mortality from the many tumours may be detected with Spiral CT than with disease has been declining over recent years, it remains conventional radiography. Most of these were stage I [11–14] the most common cause of cancer death in men, and and are therefore likely to have a good prognosis . in women mortality is second only to that of breast The United States Early Lung Cancer Action Project [14] cancer. The vast majority (>90%) of cases are caused by (ELCAP) trial reported by Henschke et al. enrolled cigarette smoking. Most patients present with advanced 1000 subjects aged 60 years or over, with at least 10 pack disease for which no curative treatment is available and years of cigarette smoking. Lung cancer was detected in [2,3] only 8–14% of patients survive 5 years . Therefore, 27 (2.7%) by CT and in seven (0.7%) by chest radiogra- novel approaches to the diagnosis and management of phy; 23 (81%) had stage I disease at diagnosis. No lung cancer are urgently required. Non-small cell lung cancers detected on chest radiography were missed on cancer, which accounts for approximately 70% of all Spiral CT. Annual repeat Spiral CT detected a further [14] lung cancers, may benefit from screening and early seven interval cancers, all stage I . Other studies from detection because surgery for stage I disease results in the Mayo Clinic and Germany have shown similar [4,5] 5-year survival rates ranging from 55% to over 80% . preliminary results. A recent report from Japan of a 3-year mass screening programme has demonstrated detection of nearly 11 times the expected annual number [15] of early lung cancers . Lung cancer screening Currently no randomized controlled trials are being It is widely accepted that the only valid means of conducted for lung cancer screening using Spiral CT as demonstrating the effect of lung cancer screening is by the intervention arm. The major issue regarding the means of a randomized controlled trial with mortality design of randomized controlled trials (RCT) of Spiral from lung cancer as the primary end-point. Four ran- CT is whether to use chest radiography or ‘no screening’ domized controlled trials of lung cancer screening were in the control arm. The major disadvantage of using performed in the 1970s, all based on chest radiography chest radiography as the control arm is that the results [6–9] together with sputum cytology . None showed evi- of such an RCT would be difficult to interpret as the dence of reduction in lung cancer mortality although benefit of chest radiography, if any, is currently un- none of the trials had sufficient statistical power to known. Furthermore, the control arm should represent exclude a modest effect. The results of these trials standard practice and in most of the European studies, formed the basis of the generally accepted view that lung including the UK, standard clinical practice is ‘no cancer screening is ineffective. screening’. 1470-7330/01/01006 + 11  2001 International Cancer Imaging Society Multidisciplinary Symposium — screening for cancer 7 Screening 20 000 186 lung cancer 40 000 deaths smokers + smoking cessation aged intervention 60 74 20 000 248 lung cancer deaths No screening 2.48 / 1000 /year Figure 1 UK Randomized Trial Design — for 5 years. The power to detect a difference of 25% at 5% level of statistical significance is 84%. [16,17] While non-randomized controlled trials will provide 10 mSv . The radiation dose of Spiral CT will be information on the frequency of detection of malig- monitored in a quality control programme by the nant nodules with Spiral CT, none are designed to physicist designated to the study. examine lung cancer mortality in a screened group in The ELCAP study showed that 23% of individuals comparison with lung cancer mortality in a control screened with Spiral CT had pulmonary nodules but group. Therefore, they will not answer the primary only 2.7% of screened individuals had lung cancer, question ‘does Spiral CT screening for lung cancer indicating a high ratio of benign to malignant nodules. reduce lung cancer mortality?’ In the United States there False-positive Spiral CT examinations or false-positive is increasing belief that Spiral CT for early lung cancer histology/cytology results from biopsy may lead to detection is likely to be beneficial, even in the absence of unnecessary lung resection, introducing the risks of proven efficacy, and demand for this service is rapidly morbidity and mortality associated with thoracic sur- increasing. Thus randomized controlled trials of Spiral gery. However, in the ELCAP study no patient with a CT are timely. At the present time it is impossible benign nodule was referred for thoracotomy. Biopsies to estimate the financial implications of screening were performed on 28 nodules and 27 of these were [14] but if Spiral CT is shown to be worthwhile, it is likely malignant . Although risks of biopsy are small, they that the health impact would be as great or greater than carry important clinical significance in elderly smokers that of breast cancer screening. Even if screening with chronic obstructive pulmonary disease. reduced lung cancer mortality by only 10% of all lung Small peripheral lung cancers may be missed on the cancers, it would represent more than double the initial Spiral CT examination although identified on a [13] number of lives saved from breast cancer screening. The subsequent scan. Kakinuma et al. reported that seven effect of Spiral CT screening may well be greater than of 22 lung cancers were missed on initial screening 10%. with Spiral CT but when detected at follow-up, six of these were stage I. Lung cancers arising in the central airways are also likely to be missed on Spiral CT as the technique is insensitive in detecting small endo-bronchial Spiral CT lesions. Single-channel Spiral CT has been used in most of the low-dose screening studies to date. However, Multi- channel CT, now being introduced widely into clinical The proposed UK Spiral CT Trial practice, provides improved fast data acquisition com- bined with excellent image quality. This new CT tech- In the UK in 1999 lung cancer was responsible for nology is unlikely to be superseded by a significant 34 240 deaths (22% of all cancer deaths). Proposals alternative in the foreseeable future and is advocated for for a randomized controlled trial have been developed all proposed screening trials. It is important to use the by the UK Cancer Coordinating Committee for most up-to-date technology because randomized con- Research — Lung (UKCCCR). The primary research trolled trials take many years to complete and advances objective of the UK trial is to determine whether lung in technology during the trial period may lead to cancer screening using low-dose Spiral CT reduces mor- criticism of the results. tality from lung cancer. To address this issue a random- Although the risk of X-radiation exposure is ized controlled trial of Spiral CT vs. no screening in an important consideration, the dose of X-radiation smokers, 60 years and over, is proposed, with lung received at Spiral CT screening is likely to be less than cancer mortality as the primary end-point. Smoking 2.5 mSv per scan, irrespective of the type of scanner cessation will be offered to both the screened and [14] used. Adopting the same protocol as Henschke et al. unscreened group. Initially a pilot trial of 2000 individ- and using a scanner of above-average dose efficiency, the uals is planned, the purpose of which is to determine the [16] patient dose is 1mSv . This compares favourably with feasibility, compliance and costs of a large randomized the average annual environmental exposure in the UK controlled trial. There will be six participating centres in of 2.2 mSv, some regions receive as much as the pilot. 8 Multidisciplinary Symposium — screening for cancer (a) Spiral CT No abnormality Pulmonary nodules ~ 800 persons ~ 200 persons Category 1 Non-calcified nodule = benign ~ 40 ~ 160 Follow-up at 1 year (b) Non-calcified nodule ~ 160 Category 2 Category 3 Category 4 5 10 mm > 10 mm ≤ 4 mm Observe growth Biopsy Follow-up at 3, 6, 9, 12 + 24 1 year Lung resection months Figure 2 Algorithm for evaluating lung nodules. It is anticipated that approximately 40 000 individuals The success of the pilot will be based upon the ability will be required in the full trial conducted over 5 years to identify eligible individuals for the trial, the number to demonstrate a reduction in lung cancer mortality recruited, and their return for a second Spiral CT scan of 25%. In the pilot we propose to perform Spiral after 1 year. This information will be used to determine CT at baseline and then at 1 year. In the full trial the size, duration and costs of the full trial, provided the Spiral CT would be performed annually for 5 years pilot is considered to be successful. In addition, the (Fig. 1). pilot will indicate the proportion of subjects who have Multidisciplinary Symposium — screening for cancer 9 nodules which require further evaluation and the pro- are frequently irregular in shape and may also grow portion of these that are cancers including observation asymmetrically. This new software, which is currently of nodule growth. The algorithm for evaluating nodules still under development, promises to be considerably is shown in Fig. 2. more accurate for assessing tumour growth. Conclusion Definition and classification of nodules Lung cancer screening is being investigated throughout A pulmonary nodule is defined as soft tissue or ground the Western world using low-dose Spiral CT and some glass opacity of rounded shape. encouraging results have already been published. A randomized controlled trial is generally accepted as the only method of demonstrating a reduction in disease- Category 1 specific mortality. However, as yet, no randomized trials Benign nodules: lesions showing central, rim, uniform or of lung cancer screening are being conducted. Proposals other benign distribution of calcification; fat attenuation for a UK randomized controlled trial of Spiral CT vs. no within the nodule, clear linear or linear branching screening are presented. densities, or known to be stable size for at least 12 months (for CT, defined as within measurement error of up to 20%). References [1] Landis SH, Murray T, Bolden S, Wingo PA. Cancer Statistics. Category 2 CA Cancer J Clin 1999; 49: 8. Micronodules, i.e. 4 mm diameter. The characteristics [2] Berrino F et al. (eds) Survival of cancer patients in Europe: the and locations of all nodules will be documented for EUROCARE Study. IARC Scientific Publications No 132. Lyon: International Agency for Research on Cancer 1995. purposes of future comparison at annual screening CT. [3] Lung Cancer and Smoking — UK. Cancer Research Campaign 1996: Cancer factsheet 11.7. [4] Mountain CF. Assessment of the role of surgery for control of Category 3 lung cancer. Ann Thorac Surg 1977; 24: 365. [5] Shah R, Sabanathan S, Richardson J, Mearns AJ, Boulden C. Indeterminate nodules of 5–10 mm diameter whose Results of surgical treatment of stage I and II lung cancer. J growth rate is, as yet, undetermined, which do not fall Cardiovasc Surg 1996; 37: 169. into Category 1. [6] Flehinger BJ, Melamed MR, Saman MB, Heelan RT, Perchick WB, Martini N. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Memorial Sloan-Kettering study. Am Rev Respir Dis Category 4 1984; 130: 555. [7] Tockman MS. Survival and mortality from lung cancer in a Nodules >10 mm diameter which do not fall into the screened population: the John Hopkins Study. Chest 1986; 89: description for benign nodules, or those <10 mm if 324S. known to be enlarging on serial CT studies. Nodule [8] Kubik A, Parkin DM, Khlat M, Erban J, Polak J, Adamec M. characteristics may include round or spiculated margins, Lack of benefit from semi-annual screening for cancer of the and cavitation. Focal areas of ground glass are also lung: follow-up report of a randomized controlled trial on a population of high-risk males in Czechoslovakia. Int J Cancer included in this category. 1990; 45: 26. All Category 3 nodules will be measured and observed [9] Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller for tumour growth at 3, 6, 9, 12 and 24 months. WE, Muhm JR. Lung cancer screening: the Mayo program. J Occup Med 1986; 28: 746. [10] Gohagan JK, Prorok PC, Kramer BS, Hayes RB, Cornett JE. The prostate, lung, colorectal and ovarian cancer screening trial of the National Cancer Institute. Cancer 1995; 75: 1869. Nodule measurement [11] Kaneko M, Eguchi K, Ohmatsu H et al. Peripheral lung cancer: screening and detection with low-dose spiral CT versus Soft tissue nodules are be measured (in mm) on standard radiography. Radiology 1996; 201: 798. lung and soft tissue windows, as defined above, using the [12] Sone S, Takashima S, Li F et al. Mass screening for lung maximum short axis (x) and long axis (y) diameters cancer with mobile spiral computed tomography scanner. taken at the widest point of the nodule. Tumour volume Lancet 1998; 351: 1242. can be calculated from the 2-dimensional measure- [13] Kakinuma R, Ohmatsu H, Kaneko M et al. Detection failures in spiral CT screening for lung cancer: analysis of CT findings. ments using the prolate eclipse formula (dimension Radiology 1999; 212: 61. x dimension y 0.52). [14] Henschke CI, McCauley DI, Yankelevitz DF et al. Early Recent research using specially designed computer Lung Cancer Action Project: overall design and findings from software (Nodview) developed by Dr A Reeves and baseline screening. Lancet 1999; 354: 99. [18] colleagues at the Weill Medical College of Cornell [15] Sone S, Li F, Yang ZG et al. Results of a three-year mass University, New York, USA, has shown that tumours screening programme for lung cancer using mobile low-dose 10 Multidisciplinary Symposium — screening for cancer spiral computed tomography scanner. Br J Cancer 2001; 84: [18] Reeves AP, Kostis WJ. Computer-aided diagnosis of small 25. pulmonary nodules. Sem Ultrasound, CT & MRI 2000; 2: [16] ImPACT CT Scanner Comparison Report Issue 12 MDA/00/ The digital object identifier for this article is: 10.1102/ [17] Living with Radiation. NRPB 1998; ISBN 0-85951-419-6; 73: 1470-7330.2001.006 Colon cancer screening Jay P Heiken Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA Colorectal cancer is a major health problem worldwide. Table 1 Recommended options for colorectal cancer Last year in the United States alone, more than 130 000 screening in asymptomatic, average-risk individuals* people were diagnosed with colorectal cancer and more [1] Starting at age 50 than 56 000 died of their disease . Fortunately, this Annual FOBT† neoplasm is highly suited to screening because of its long Flexible sigmoidoscopy every 5 years preclinical phase, during which it is detectable and Annual FOBT and sigmoidoscopy every 5 years [2] curable . Nevertheless, screening programs for colorec- Colonoscopy every 10 years tal cancer have been only partly successful, owing Double-contrast barium enema every 5–10 years largely to poor patient compliance with screening rec- [3,4] ommendations . A number of organizations including *Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; the World Health Organization (WHO), the American 112: 594–642. Cancer Society (ACS), the Agency for Health Care †The American Cancer Society does not recommend fecal occult Policy and Research (AHCPR), the US Preventive blood testing (FOBT) by itself. Service Task Force (USPSTF), and the American Gastroenterology Association (AGA) have issued or endorsed guidelines for colorectal cancer screening. This review summarizes the clinical evidence supporting Fecal occult blood testing colorectal cancer screening in the average-risk popula- Fecal occult blood testing (FOBT) is the safest and tion and in high-risk groups, discusses the advantages least expensive of the currently available screening and disadvantages of the available screening tests, and tests. Three prospective, randomized, controlled trials outlines the currently recommended guidelines for have demonstrated the effectiveness of FOBT in screening based on risk category. [7–9] reducing colorectal cancer mortality by 15% to 33% . However, its benefit in reducing colorectal mortality is attributed not only to early cancer detection but also to the incidental discovery and removal of adenomatous Average-risk population polyps at subsequent colonoscopy. Such chance discov- Average-risk patients are asymptomatic individuals aged ery of adenomatous polyps and non-bleeding cancers by 50 years of age or older who have no personal or family colonoscopy has been estimated to account for 16–25% history of colorectal cancer or adenomatous polyps and of the colorectal cancer deaths prevented by the use of [10] no history of inammatory bowel disease. The two most FOBT . Limitations of FOBT include its relatively recently published screening recommendations, those of low sensitivity for detecting cancers and its inability to [5] [6] [11] the ACS and AHCPR , present guidelines for screen- detect the vast majority of adenomas . Because colo- ing average-risk patients in the form of lists of options rectal cancers bleed intermittently, 50% or more of (Table 1). The options include annual fecal occult blood patients with colorectal cancer may have a negative [11,12] test (not included as a stand alone test in the ACS test result . Thus, to be effective, FOBT must be guidelines), exible sigmoidoscopy every 5 years, annual administered annually or biennially, which makes fecal occult blood test plus exible sigmoidoscopy every patient compliance a problem. Furthermore, the positive 5 years, double-contrast barium enema every 5 to 10 predictive value of FOBT is only approximately [11,12] years, and colonoscopy every 10 years. 10% . http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Imaging Springer Journals

Proposals for lung cancer screening in the UK

Husband, Janet
Cancer Imaging , Volume 2 (1) – May 5, 2015
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Springer Journals
Copyright
Copyright © 2001 by International Cancer Imaging Society
Subject
Medicine & Public Health; Imaging / Radiology; Cancer Research; Oncology
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1470-7330
DOI
10.1102/1470-7330.2001.006
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Abstract

Cancer Imaging (2001) 2, 6–16 Multidisciplinary Symposium — Screening for Cancer Monday 15 October 2001, 10.20–12.45 Janet E Husband Academic Department of Diagnostic Radiology, The Royal Marsden NHS Trust, Downs Road, Sutton, Surrey SM2 5PT, UK Lung cancer is the most frequent cause of cancer death in The National Cancer Institute is reassessing the role the Western world. Low dose Spiral CT offers a new of chest radiography in a large randomized controlled approach to lung cancer detection and early results from trial, the Prostate–Lung–Colorectal–Ovarian (PLCO) screening studies are promising. United Kingdom proposals Trial, which is designed to have sufficient statistical for a randomized controlled trial of lung cancer screening power to identify a reduction in lung cancer mortality of [10] of spiral CT vs. a control arm of no screening is discussed. 10% . While chest radiography may identify lung lesions greater than 1 cm in diameter, Spiral CT can identify pulmonary nodules less than 5 mm in diameter. This has opened the way for the use of Spiral CT in early Introduction detection of peripheral lung cancers. Lung cancer is now the leading cause of cancer death in Early results from non-randomized trials in Japan the Western world and accounts for more deaths than and the United States using Spiral CT for screening lung the total from colon, lung and prostate cancer combined cancer have shown that approximately four times as [1] in the United States . Although mortality from the many tumours may be detected with Spiral CT than with disease has been declining over recent years, it remains conventional radiography. Most of these were stage I [11–14] the most common cause of cancer death in men, and and are therefore likely to have a good prognosis . in women mortality is second only to that of breast The United States Early Lung Cancer Action Project [14] cancer. The vast majority (>90%) of cases are caused by (ELCAP) trial reported by Henschke et al. enrolled cigarette smoking. Most patients present with advanced 1000 subjects aged 60 years or over, with at least 10 pack disease for which no curative treatment is available and years of cigarette smoking. Lung cancer was detected in [2,3] only 8–14% of patients survive 5 years . Therefore, 27 (2.7%) by CT and in seven (0.7%) by chest radiogra- novel approaches to the diagnosis and management of phy; 23 (81%) had stage I disease at diagnosis. No lung cancer are urgently required. Non-small cell lung cancers detected on chest radiography were missed on cancer, which accounts for approximately 70% of all Spiral CT. Annual repeat Spiral CT detected a further [14] lung cancers, may benefit from screening and early seven interval cancers, all stage I . Other studies from detection because surgery for stage I disease results in the Mayo Clinic and Germany have shown similar [4,5] 5-year survival rates ranging from 55% to over 80% . preliminary results. A recent report from Japan of a 3-year mass screening programme has demonstrated detection of nearly 11 times the expected annual number [15] of early lung cancers . Lung cancer screening Currently no randomized controlled trials are being It is widely accepted that the only valid means of conducted for lung cancer screening using Spiral CT as demonstrating the effect of lung cancer screening is by the intervention arm. The major issue regarding the means of a randomized controlled trial with mortality design of randomized controlled trials (RCT) of Spiral from lung cancer as the primary end-point. Four ran- CT is whether to use chest radiography or ‘no screening’ domized controlled trials of lung cancer screening were in the control arm. The major disadvantage of using performed in the 1970s, all based on chest radiography chest radiography as the control arm is that the results [6–9] together with sputum cytology . None showed evi- of such an RCT would be difficult to interpret as the dence of reduction in lung cancer mortality although benefit of chest radiography, if any, is currently un- none of the trials had sufficient statistical power to known. Furthermore, the control arm should represent exclude a modest effect. The results of these trials standard practice and in most of the European studies, formed the basis of the generally accepted view that lung including the UK, standard clinical practice is ‘no cancer screening is ineffective. screening’. 1470-7330/01/01006 + 11  2001 International Cancer Imaging Society Multidisciplinary Symposium — screening for cancer 7 Screening 20 000 186 lung cancer 40 000 deaths smokers + smoking cessation aged intervention 60 74 20 000 248 lung cancer deaths No screening 2.48 / 1000 /year Figure 1 UK Randomized Trial Design — for 5 years. The power to detect a difference of 25% at 5% level of statistical significance is 84%. [16,17] While non-randomized controlled trials will provide 10 mSv . The radiation dose of Spiral CT will be information on the frequency of detection of malig- monitored in a quality control programme by the nant nodules with Spiral CT, none are designed to physicist designated to the study. examine lung cancer mortality in a screened group in The ELCAP study showed that 23% of individuals comparison with lung cancer mortality in a control screened with Spiral CT had pulmonary nodules but group. Therefore, they will not answer the primary only 2.7% of screened individuals had lung cancer, question ‘does Spiral CT screening for lung cancer indicating a high ratio of benign to malignant nodules. reduce lung cancer mortality?’ In the United States there False-positive Spiral CT examinations or false-positive is increasing belief that Spiral CT for early lung cancer histology/cytology results from biopsy may lead to detection is likely to be beneficial, even in the absence of unnecessary lung resection, introducing the risks of proven efficacy, and demand for this service is rapidly morbidity and mortality associated with thoracic sur- increasing. Thus randomized controlled trials of Spiral gery. However, in the ELCAP study no patient with a CT are timely. At the present time it is impossible benign nodule was referred for thoracotomy. Biopsies to estimate the financial implications of screening were performed on 28 nodules and 27 of these were [14] but if Spiral CT is shown to be worthwhile, it is likely malignant . Although risks of biopsy are small, they that the health impact would be as great or greater than carry important clinical significance in elderly smokers that of breast cancer screening. Even if screening with chronic obstructive pulmonary disease. reduced lung cancer mortality by only 10% of all lung Small peripheral lung cancers may be missed on the cancers, it would represent more than double the initial Spiral CT examination although identified on a [13] number of lives saved from breast cancer screening. The subsequent scan. Kakinuma et al. reported that seven effect of Spiral CT screening may well be greater than of 22 lung cancers were missed on initial screening 10%. with Spiral CT but when detected at follow-up, six of these were stage I. Lung cancers arising in the central airways are also likely to be missed on Spiral CT as the technique is insensitive in detecting small endo-bronchial Spiral CT lesions. Single-channel Spiral CT has been used in most of the low-dose screening studies to date. However, Multi- channel CT, now being introduced widely into clinical The proposed UK Spiral CT Trial practice, provides improved fast data acquisition com- bined with excellent image quality. This new CT tech- In the UK in 1999 lung cancer was responsible for nology is unlikely to be superseded by a significant 34 240 deaths (22% of all cancer deaths). Proposals alternative in the foreseeable future and is advocated for for a randomized controlled trial have been developed all proposed screening trials. It is important to use the by the UK Cancer Coordinating Committee for most up-to-date technology because randomized con- Research — Lung (UKCCCR). The primary research trolled trials take many years to complete and advances objective of the UK trial is to determine whether lung in technology during the trial period may lead to cancer screening using low-dose Spiral CT reduces mor- criticism of the results. tality from lung cancer. To address this issue a random- Although the risk of X-radiation exposure is ized controlled trial of Spiral CT vs. no screening in an important consideration, the dose of X-radiation smokers, 60 years and over, is proposed, with lung received at Spiral CT screening is likely to be less than cancer mortality as the primary end-point. Smoking 2.5 mSv per scan, irrespective of the type of scanner cessation will be offered to both the screened and [14] used. Adopting the same protocol as Henschke et al. unscreened group. Initially a pilot trial of 2000 individ- and using a scanner of above-average dose efficiency, the uals is planned, the purpose of which is to determine the [16] patient dose is 1mSv . This compares favourably with feasibility, compliance and costs of a large randomized the average annual environmental exposure in the UK controlled trial. There will be six participating centres in of 2.2 mSv, some regions receive as much as the pilot. 8 Multidisciplinary Symposium — screening for cancer (a) Spiral CT No abnormality Pulmonary nodules ~ 800 persons ~ 200 persons Category 1 Non-calcified nodule = benign ~ 40 ~ 160 Follow-up at 1 year (b) Non-calcified nodule ~ 160 Category 2 Category 3 Category 4 5 10 mm > 10 mm ≤ 4 mm Observe growth Biopsy Follow-up at 3, 6, 9, 12 + 24 1 year Lung resection months Figure 2 Algorithm for evaluating lung nodules. It is anticipated that approximately 40 000 individuals The success of the pilot will be based upon the ability will be required in the full trial conducted over 5 years to identify eligible individuals for the trial, the number to demonstrate a reduction in lung cancer mortality recruited, and their return for a second Spiral CT scan of 25%. In the pilot we propose to perform Spiral after 1 year. This information will be used to determine CT at baseline and then at 1 year. In the full trial the size, duration and costs of the full trial, provided the Spiral CT would be performed annually for 5 years pilot is considered to be successful. In addition, the (Fig. 1). pilot will indicate the proportion of subjects who have Multidisciplinary Symposium — screening for cancer 9 nodules which require further evaluation and the pro- are frequently irregular in shape and may also grow portion of these that are cancers including observation asymmetrically. This new software, which is currently of nodule growth. The algorithm for evaluating nodules still under development, promises to be considerably is shown in Fig. 2. more accurate for assessing tumour growth. Conclusion Definition and classification of nodules Lung cancer screening is being investigated throughout A pulmonary nodule is defined as soft tissue or ground the Western world using low-dose Spiral CT and some glass opacity of rounded shape. encouraging results have already been published. A randomized controlled trial is generally accepted as the only method of demonstrating a reduction in disease- Category 1 specific mortality. However, as yet, no randomized trials Benign nodules: lesions showing central, rim, uniform or of lung cancer screening are being conducted. Proposals other benign distribution of calcification; fat attenuation for a UK randomized controlled trial of Spiral CT vs. no within the nodule, clear linear or linear branching screening are presented. densities, or known to be stable size for at least 12 months (for CT, defined as within measurement error of up to 20%). References [1] Landis SH, Murray T, Bolden S, Wingo PA. Cancer Statistics. Category 2 CA Cancer J Clin 1999; 49: 8. Micronodules, i.e. 4 mm diameter. The characteristics [2] Berrino F et al. (eds) Survival of cancer patients in Europe: the and locations of all nodules will be documented for EUROCARE Study. IARC Scientific Publications No 132. Lyon: International Agency for Research on Cancer 1995. purposes of future comparison at annual screening CT. [3] Lung Cancer and Smoking — UK. Cancer Research Campaign 1996: Cancer factsheet 11.7. [4] Mountain CF. Assessment of the role of surgery for control of Category 3 lung cancer. Ann Thorac Surg 1977; 24: 365. [5] Shah R, Sabanathan S, Richardson J, Mearns AJ, Boulden C. Indeterminate nodules of 5–10 mm diameter whose Results of surgical treatment of stage I and II lung cancer. J growth rate is, as yet, undetermined, which do not fall Cardiovasc Surg 1996; 37: 169. into Category 1. [6] Flehinger BJ, Melamed MR, Saman MB, Heelan RT, Perchick WB, Martini N. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Memorial Sloan-Kettering study. Am Rev Respir Dis Category 4 1984; 130: 555. [7] Tockman MS. Survival and mortality from lung cancer in a Nodules >10 mm diameter which do not fall into the screened population: the John Hopkins Study. Chest 1986; 89: description for benign nodules, or those <10 mm if 324S. known to be enlarging on serial CT studies. Nodule [8] Kubik A, Parkin DM, Khlat M, Erban J, Polak J, Adamec M. characteristics may include round or spiculated margins, Lack of benefit from semi-annual screening for cancer of the and cavitation. Focal areas of ground glass are also lung: follow-up report of a randomized controlled trial on a population of high-risk males in Czechoslovakia. Int J Cancer included in this category. 1990; 45: 26. All Category 3 nodules will be measured and observed [9] Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller for tumour growth at 3, 6, 9, 12 and 24 months. WE, Muhm JR. Lung cancer screening: the Mayo program. J Occup Med 1986; 28: 746. [10] Gohagan JK, Prorok PC, Kramer BS, Hayes RB, Cornett JE. The prostate, lung, colorectal and ovarian cancer screening trial of the National Cancer Institute. Cancer 1995; 75: 1869. Nodule measurement [11] Kaneko M, Eguchi K, Ohmatsu H et al. Peripheral lung cancer: screening and detection with low-dose spiral CT versus Soft tissue nodules are be measured (in mm) on standard radiography. Radiology 1996; 201: 798. lung and soft tissue windows, as defined above, using the [12] Sone S, Takashima S, Li F et al. Mass screening for lung maximum short axis (x) and long axis (y) diameters cancer with mobile spiral computed tomography scanner. taken at the widest point of the nodule. Tumour volume Lancet 1998; 351: 1242. can be calculated from the 2-dimensional measure- [13] Kakinuma R, Ohmatsu H, Kaneko M et al. Detection failures in spiral CT screening for lung cancer: analysis of CT findings. ments using the prolate eclipse formula (dimension Radiology 1999; 212: 61. x dimension y 0.52). [14] Henschke CI, McCauley DI, Yankelevitz DF et al. Early Recent research using specially designed computer Lung Cancer Action Project: overall design and findings from software (Nodview) developed by Dr A Reeves and baseline screening. Lancet 1999; 354: 99. [18] colleagues at the Weill Medical College of Cornell [15] Sone S, Li F, Yang ZG et al. Results of a three-year mass University, New York, USA, has shown that tumours screening programme for lung cancer using mobile low-dose 10 Multidisciplinary Symposium — screening for cancer spiral computed tomography scanner. Br J Cancer 2001; 84: [18] Reeves AP, Kostis WJ. Computer-aided diagnosis of small 25. pulmonary nodules. Sem Ultrasound, CT & MRI 2000; 2: [16] ImPACT CT Scanner Comparison Report Issue 12 MDA/00/ The digital object identifier for this article is: 10.1102/ [17] Living with Radiation. NRPB 1998; ISBN 0-85951-419-6; 73: 1470-7330.2001.006 Colon cancer screening Jay P Heiken Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA Colorectal cancer is a major health problem worldwide. Table 1 Recommended options for colorectal cancer Last year in the United States alone, more than 130 000 screening in asymptomatic, average-risk individuals* people were diagnosed with colorectal cancer and more [1] Starting at age 50 than 56 000 died of their disease . Fortunately, this Annual FOBT† neoplasm is highly suited to screening because of its long Flexible sigmoidoscopy every 5 years preclinical phase, during which it is detectable and Annual FOBT and sigmoidoscopy every 5 years [2] curable . Nevertheless, screening programs for colorec- Colonoscopy every 10 years tal cancer have been only partly successful, owing Double-contrast barium enema every 5–10 years largely to poor patient compliance with screening rec- [3,4] ommendations . A number of organizations including *Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; the World Health Organization (WHO), the American 112: 594–642. Cancer Society (ACS), the Agency for Health Care †The American Cancer Society does not recommend fecal occult Policy and Research (AHCPR), the US Preventive blood testing (FOBT) by itself. Service Task Force (USPSTF), and the American Gastroenterology Association (AGA) have issued or endorsed guidelines for colorectal cancer screening. This review summarizes the clinical evidence supporting Fecal occult blood testing colorectal cancer screening in the average-risk popula- Fecal occult blood testing (FOBT) is the safest and tion and in high-risk groups, discusses the advantages least expensive of the currently available screening and disadvantages of the available screening tests, and tests. Three prospective, randomized, controlled trials outlines the currently recommended guidelines for have demonstrated the effectiveness of FOBT in screening based on risk category. [7–9] reducing colorectal cancer mortality by 15% to 33% . However, its benefit in reducing colorectal mortality is attributed not only to early cancer detection but also to the incidental discovery and removal of adenomatous Average-risk population polyps at subsequent colonoscopy. Such chance discov- Average-risk patients are asymptomatic individuals aged ery of adenomatous polyps and non-bleeding cancers by 50 years of age or older who have no personal or family colonoscopy has been estimated to account for 16–25% history of colorectal cancer or adenomatous polyps and of the colorectal cancer deaths prevented by the use of [10] no history of inammatory bowel disease. The two most FOBT . Limitations of FOBT include its relatively recently published screening recommendations, those of low sensitivity for detecting cancers and its inability to [5] [6] [11] the ACS and AHCPR , present guidelines for screen- detect the vast majority of adenomas . Because colo- ing average-risk patients in the form of lists of options rectal cancers bleed intermittently, 50% or more of (Table 1). The options include annual fecal occult blood patients with colorectal cancer may have a negative [11,12] test (not included as a stand alone test in the ACS test result . Thus, to be effective, FOBT must be guidelines), exible sigmoidoscopy every 5 years, annual administered annually or biennially, which makes fecal occult blood test plus exible sigmoidoscopy every patient compliance a problem. Furthermore, the positive 5 years, double-contrast barium enema every 5 to 10 predictive value of FOBT is only approximately [11,12] years, and colonoscopy every 10 years. 10% .

Journal

Cancer Imaging – Springer Journals

Published: May 5, 2015

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