Zusammenfassung
Neben Zigarettenrauch als Hauptursache für die Entstehung des Lungenkarzinoms spielen
bei der Karzinogenese auch berufliche Expositionen, vorrangig gegenüber Asbest, polyzyklischen
aromatischen Kohlenwasserstoffen, Uran, und silikogenen Stäuben eine wichtige Rolle.
Mangels flächendeckender Wirksamkeit von Maßnahmen zur Verminderung des Rauchens stellt
sich die Frage nach Screeningmöglichkeiten für das Lungenkarzinom. Verschiedene epidemiologische
Fallstricke sind bei der Bewertung der Wirksamkeit von Screeningtests zu berücksichtigen.
Die Ergebnisse der großen Screening-Studien mit konventioneller Bildgebung, Sputumzytologie
und Low-dose-Computertomographie werden vergleichend gegenübergestellt. Bislang liegen
keine Ergebnisse randomisierter kontrollierter Studien mit Low-dose-CT-Screening vor,
laufende Studien umfassen derzeit etwa 100 000 Personen. Erst am Ende dieses Jahrzehnts
wird man daher absehen können, ob ein Lungenkarzinom-Screening unter Einsatz neuer
Techniken wissenschaftlich zu befürworten ist. Sofern die in den Machbarkeitsstudien
eingesetzten diagnostischen Algorithmen Anwendung finden, liegt schon jetzt die Quote
invasiver Maßnahmen, die benigne Läsionen ergaben, im Mittel bei 34 % und damit niedriger
als beispielsweise in Screening-Programmen für das Mammakarzinom.
Abstract
Besides smoking as the main risk factor for lung cancer several occupational risk
factors like exposure to asbestos, polycyclic aromatic hydrocarbons, uranium and dust
containing nickel or silica have to be considered. Due to lack of effort in smoking
prevention and cessation, lung cancer screening is an important issue. A number of
pitfalls has to be considered when evaluating the efficacy of screening procedures.
In this paper, we summarize the results of the major studies including chest X-ray,
sputum cytology and low dose computed tomography. Randomized controlled studies involving
low dose CT in about 100 000 subjects are on the way. Around the year 2010 we will
be able to define whether or not lung cancer screening including new techniques and
standardized algorithms yields a decrease in mortality. If diagnostic algorithms are
used which have been applied in published feasibility studies, the mean percentage
of invasive diagnostic measures revealing benign lesions is about 34 % and thus below
those obtained in, e. g., breast cancer screening trials.
Literatur
- 1
Greenlee R T, Murray T, Bolden S. et al .
Cancer statistics.
CA Cancer J Clin.
2000;
50
7-33
- 2 Arbeitsgemeinschaft bevölkerungsbezogener Krebsregister in Deutschland, in Zusammenarbeit
mit dem Robert-Koch-Institut .„Krebs in Deutschland”, 3.Ausgabe. Saarbrücken 2002
- 3
Peto R, Darby S, Deo H. et al .
“Smoking, smoking cessation, and lung cancer in the UK since 1950”.
BMJ.
2000;
321
323-329
- 4 Lorenz D. mit einem Beitrag von Nowak D .Checkliste XXL Pneumologie. Stuttgart:
Thieme 2004
- 5
Schön S, Nowak D.
Medikamentöse Verfahren zur Raucherentwöhnung.
Suchtmed.
2002;
4
189-199
- 6 American Cancer Society .Cancer facts and figures. Atlanta: ACS 2001
- 7
Diderich A S, Lenzen H.
Radiation exposure associated with imaging of the chest: Comparison of different radiographic
and computed tomography techniques.
Cancer.
2000;
89
2457-2460
- 8
Humphrey L L, Teutsch S, Johnson M.
Lung cancer screening with sputum cytologic examination, chest radiography, and computed
tomography: an update for the U.S. Preventive Services Task Force.
Ann Intern Med.
2004;
140
740-753
- 9
Becker N.
Screening aus epidemiologischer Sicht.
Radiologe.
2002;
42
592-600
- 10
Patz Jr E F, Goodman P C, Bepler G.
Screening for lung cancer.
N Engl J Med.
2000;
343
1627-1633
- 11
Eddy D M.
Screening for lung cancer.
Ann Intern Med.
1989;
111
232-237
- 12
Strauss G M.
The Mayo lung cohort: a regression analysis focusing on lung cancer incidence and
mortality.
J Clin Oncol.
2002;
20
1973-1983
- 13
Bepler G, Carney D G, Djulbegovic B. et al .
A systematic review and lessons learned from early lung cancer detection trials using
low-dose computed tomography of the chest.
Cancer Control.
2003;
10
306-313
- 14
Manser R L, Irving L B, Byrnes G. et al .
Screening for lung cancer: a systematic review and meta-analysis of controlled trials.
Thorax.
2003;
58
784-789
- 15
Van Klaveren R J, Habbema J DF, Pedersen J H. et al .
Lung cancer screening by low-dose spiral computed tomography.
Eur Respir J.
2001;
18
857-866
- 16
Diederich S, Wormanns D, Heindel W.
Lungenkrebsfrüherkennung mit Low-dose-CT: ein Update.
Radiologe.
42;
2002
608-611
- 17
Diederich S, Wormanns D, Heindel W.
Lung cancer screening with low-dose CT.
Eur J Radiol.
2003;
45
2-7
- 18
Wilde J.
A 10 year follow-up of semi-annual screening for early detection of lung cancer in
the Erfurt County, GDR.
Eur Respir J.
1989;
2
656-662
- 19
Brett G Z.
The value of lung cancer detection by six-monthly chest radiographs.
Thorax.
1968;
23
414-420
- 20
Brett G.
Earlier diagnosis and survival in lung cancer.
BMJ.
1969;
4
260-262
- 21
Fontana R S, Sanderson D R, Woolner L B. et al .
Lung cancer screening: the Mayo program.
J Occup Med.
1986;
28
746-750
- 22
Fontana R S, Sanderson D R, Woolner L B. et al .
Screening for lung cancer. A critique of the Mayo Lung project.
Cancer.
1991;
67 (4 suppl)
1155-1164
- 23
Marcus P, Bergstralh E J, Fagerström R M. et al .
Lung cancer mortality in the Mayo Lung project: impact of extended follow-up.
J Natl Cancer Inst.
2000;
92
1308-1316
- 24
Friedman G, Collen M F, Fireman B H.
Multiplhasic health check up evaluation: a 16 year follow up.
J Chron Dis.
1986;
39
453-463
- 25
Kubik A, Polak J.
Lung cancer detection: results of a randomized prospective study in Czechoslovakia.
Cancer.
1986;
57
2427-2437
- 26
Kubik A, Parkin D M, Khlat M. et al .
Lack of benefit from semi-annual screening for cancer of the lung: follow-up report
of a randomised controlled trial on a population of high-risk males in Czechoslovakia.
Int J Cancer.
1990;
45
26-33
- 27
Melamed M R, Flehinger B J, Zaman M B. et al .
Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in
New York.
Chest.
1984;
86
44-53
- 28 Tockman M, Frost J K, Stitik F P. et al .Screening and detection of lung cancer. In:
Aisner J (Hrsg) Lung cancer. New York: Churchill Livingstone 1985: 25-40
- 29
Henschke C I, McCauley D I, Yankelevitz D F. et al .
Early Lung Cancer Action Project: overall design and findings from baseline screening.
Lancet.
1999;
354
99-105
- 30
Henschke C I, McCauley D I, Yankelevitz D F. et al .
Early Lung Cancer Action Project: Initial findings on repeat screening.
Cancer.
2001;
92
153-159
- 31
Sone S, Li F, Yang Z G. et al .
Results of three-year mass screening programme for lung cancer using mobile low-dose
spiral computed tomography scanner.
Br J Cancer.
2001;
84
25-32
- 32
Sone S, Takashima S, Li F. et al .
Mass screening for lung cancer with mobile spiral computed tomography scanner.
Lancet.
1998;
351 (9111)
1242-1245
- 33
Diederich S, Wormanns D, Semik M. et al .
Screening for early lung cancer with low-dose spiral CT: prevalence in 817 asymptomatic
smokers.
Radiology.
2002;
222
773-781
- 34
Diederich S, Thomas M, Semik M. et al .
Screening for early low-dose spiral computed tomography: results of annual follow-up
examinations in asymptomatic smokers.
Eur Radiol.
2004;
14
691-702
- 35
Nawa T, Nakagawa T, Kusano S. et al .
Lung cancer screening using low-dose spiral CT: results of baseline and 1-year follow
up studies.
Chest.
2002;
122
15-20
- 36
Sobue T, Moriyama N, Kaneko M. et al .
Screening for lung cancer with low-dose helical computed tomography: anti-lung cancer
association project.
J Clin Oncol.
2002;
20
911-920
- 37
Swensen S J, Jett J R, Sloan J A. et al .
Screening for lung cancer with low-dose spiral computed tomography.
Am J Respir Crit Care Med.
2002;
165
508-513
- 38
Swensen S J, Jett J R, Sloan J A. et al .
Lung cancer screening with CT: Mayo Clinic experience.
Radiology.
2003;
226
756-761
- 39
Swensen S J, Crestanello J A, Allen M S. et al .
Thoracic surgical operations in patients enrolled in a computed tomographic screening
trial.
J Thorac Cardiovas Surg.
2004 Aug;
128 (2)
254-259
- 40
Pastorino U, Bellomi M, Landoni C. et al .
Early lung-cancer detection with spiral CT and positron emission tomography in heavy
smokers: 2-year results.
Lancet.
2003;
362
593-597
- 41
Tiitola M, Kivisari L, Huuskonen M S. et al .
Computed tomography screening for lung cancer in asbestos-exposed workers.
Lung Cancer.
2002;
35
17-22
- 42 Karp D D, Mulshine J L, Henschke C I. Non-small cell lung cancer: screening, new
imaging and prevention. In: Perry MC (Hrsg) American Society of Clinical Oncology.
Educational Book. Philadelphia: WB Saunders Co 2000: 487-502
- 43
Risse E KJ, Vooijs G P, Hof M A van't.
Diagnostic significance of “severe dysplasia” in sputum cytology.
Acta Cytol.
1988;
32
629-634
- 44
Venmans B JW, Boxem T JM van, Smit E F. et al .
Outcome of bronchial carcinoma in situ.
Chest.
2000;
117
1572-1576
- 45
Marek W, Kotschy-Lang N, Muti A. et al .
Can semi-atumated image cytometry on induced sputum become a screening tool for lung
cancer? Evaluation of quantitative semi-automated sputum cytometry on radon- and uranium-exposed
workers.
Eur Respir J.
2001;
18
942-950
- 46
Hirsch F R, Franklin W A, Gazdar A F. et al .
Early detection of lung cancer: clinical perspectives of recent advances in biology
and radiology.
Clin Cancer Res.
2001;
7
5-22
- 47
Hirsch F R, Pridiville S A, Miller Y E. et al .
Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions:
a randomized study.
J Natl Cancer Inst.
2001;
43
1385-1391
- 48
Tockman M S, Gupta P K, Myers J D. et al .
Sensitive and specific monoclonal antibody recognition of human lung cancer antigen
on preserved sputum cells: a new approach to early lung cancer detection.
J Clin Oncol.
1988;
6
1685-1693
- 49
Qiao Y-L, Tockman M S, Li L. et al .
A case-cohort study of an early biomarker of lung cancer in a screening cohort of
Yunnan tin miners in China.
Cancer Epidemiol Biomarkers Prev.
1997;
6
893-900
- 50
Tockman M S, Mulshine J L, Piantadosi S. et al .
Prospective detection of preclinical lung cancer: results from two studies of heterogeneous
nuclear ribonucleoprotein A2/B1 overexpression.
Clin Cancer Res.
1997;
3
2237-2246
- 51
Gazdar A F, Minna J D.
Molecular detection of early lung cancer.
J Natl Cancer Inst.
1999;
91
299-301
- 52
Mao L, Hruban R H, Boyle J O. et al .
Detection of oncogene mutations in sputum precedes diagnosis of lung cancer.
Cancer Res.
1994;
54
1634-1637
- 53
Miozzo M, Sozzi G, Musso K. et al .
Microsatellite alterations in bronchial and sputum specimens of lung cancer patients.
Cancer Res.
1996;
56
2285-2288
- 54
Kersting M, Friedl C, Kraus A. et al .
Differential frequencies of p16INK4 a promotor hypermethylation, p53 mutation and
K-ras mutation in exfoliative material mark the development of lung cancer in symptomatic
chronic smokers.
J Clin Oncol.
2000;
18
3222-3229
- 55
Virmani A K, Rathi A, Zöchbauer-Müller S. et al .
Promoter methylation and silencing of the retinoic acid receptor gene in lung carcinomas.
J Natl Cancer Inst.
2000;
92
1303-1307
- 56
Zöchbauer-Müller S, Fong K M, Virmani A K. et al .
Aberrant promoter methylation of multiple genes in non-small cell lung cancers.
Cancer Res.
2001;
61
249-255
- 57
Payne P W, Sebo T J, Doudkine A. et al .
Sputum screening by quantitative microscopy: a reexamination of a portion of the National
Cancer Institute Cooperative Early Lung Cancer Study.
Mayo Clin Proc.
1997;
72
697-704
- 58 Lam S, MacAulay C. Endoscopic detection of preneoplastic lesions. In: Brambilla
C, Brambilla E (Hrsg). Lung Tumors. Fundamental Biology and Clinical Management. Grenoble:
Marcel Dekker 1999: 473-480
- 59
Palcic B, Garner D M, Beveridge J. et al .
Increase of sensitivity of sputum cytology using high-resolution image cytometry:
field study results.
Cytometry.
2002;
50
168-176
- 60
McWilliams A, Mayo J, MacDonald S. et al .
Lung cancer screening. A different paradigm.
Am J Respir Crit Care Med.
2003;
168
1167-1173
- 61
Field J K, Brambilla C, Caporaso N. et al .
Consensus statements from the Second International Lung Cancer Molecular Biomarkers
Workshop: a European strategy for developing lung cancer molecular diagnostics in
high risk populations.
Int J Oncol.
2002;
21
369-373
- 62
Thunissen F BJM.
Sputum examination for early detection of lung cancer.
J Clin Pathol.
2003;
56
805-810
- 63
Woolner L B, Fontana R S, Cortesse D A. et al .
Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity
during a 10-year period.
Mayo Clin Proc.
1984;
59
453-466
- 64
Huber R M, Gamarra F, Hautmann H. et al .
5-Aminolaevulinic acid (ALA) for the fluorescence detection of bronchial tumors.
Diagnostic and Therapeutic Endoscopy.
1999;
5
113-118
- 65
Schneider J, Peltri G, Bitterlich N. et al .
Fuzzy logic-based tumor marker profiles including a new marker tumor M2-PK improved
sensitivity to the detection of progression in lung cancer patients.
Anticancer Res.
2003;
23
899-906
- 66
Nowak D, Magnussen H, Rüdiger H W.
Exposition und Disposition in der Genese des Bronchialkarzinoms 43.
Prax Klin Pneumol.
1989;
43
135-146
- 67 Nowak D. Anforderungen an Nachuntersuchungen bei anerkannter BK 4301/4302. In:
Hauptverband der gewerblichen Berufsgenossenschaften (Hrsg): Die Bedeutung von nachgehenden
Untersuchungen von Berufskrankheiten, ISBN3-88 383-638-9. 2003: 63-75
- 68
Kim Y H, Lee K S, Primack S L. et al .
Small pulmonary nodules on CT accompanying surgically resectable lung cancer: likelihood
of malignancy.
J Thoracic Imaging.
2002;
17
40-46
- 69
Miettinen O, Henschke C.
CT screening for lung cancer: coping with nihilistic recommendations.
Radiology.
2001;
221
592-596
- 70
Patz E F, Black W C, Goodmann P C.
CT screening for lung cancer: not ready for routine practice.
Radiology.
2001;
221
587-591
- 71
Patz E F, Black W C, Goodmann P C.
Commentary on Drs Miettinen und Henschke's Viewpoint.
Radiology.
2001;
221
597
- 72
Miettinen O S, Henschke C I.
Commentary on Drs Patz, Black and Goodmann's Viewpoint.
Radiology.
2001;
221
598-599
Prof. Dr. med. Dennis Nowak
Institut und Poliklinik für Arbeits- und Umweltmedizin der Universität München
Ziemssenstr. 1
80336 München
Email: dennis.nowak@med.uni-muenchen.de
