roentgenographic chest screening in the detection and survival of patients with lung cancer

Roentgenographic Chest Screening in the Detection and Survival of Patients with Lung Cancer Cooperative Study Group for Early Detection of Lung Cancer in the German Democratic Republic

ABSTRACT In the German Democratic Republic (GDR), annual mass roentgenographic screening of the chest was introduced twenty years ago. To ascertain its value in the detection of lung cancer, data were collected about treatment results at the coun- try's main chest clinics. The study covers 13,293 operations and 10,838 resections, accounting for nearly 90% of all patients with lung cancer treated surgically in the GDR from 1949 to 1974.

From 1965 to 1968, the five-year survival was more favorable in patients who were screened than in those who were diagnosed after clinical symptoms had appeared (36% for the former, 29% for the latter). For improvement of overall results, we recom- mend differentiated regular chest roentgenographic screening of men 40 to 70 years of age, individualized on the basis of tobacco usage, and full exploitation of all diagnostic and surgical tools now available.

Early detection is now recognized as a funda- mental factor in the successful treatment of cancer. However, the chances for early detection and radical treatment vary depending on the location of the tumor.

In the German Democratic Republic (GDR), annual roentgenographic screening of the chest was introduced for the detection of tuberculosis of the lung nearly twenty years ago. Since 1962 it has been obligatory, and 90% of the adult population have had a chest roentgenogram once a year [lo]. As a result of this measure, there has been a steady rise in the number of asymptomatic cancers diagnosed by screening, with an accompanying increase in resection and survival rates [6, 7, 131. Despite these facts, the general opinion still holds that roentgeno-

Accepted for publication Dec 19, 1977.

Address reprint requests to Prof Dr Widow, Zentralinstitut fur Krebsforschung der Akademie der Wissenschaften der DDR, DDR-1115 Berlin-Buch, Lindenberger Weg 80, Ger- man Democratic Republic.

graphic chest screening has no specific value in the early detection and treatment of lung cancer.

Materials and Results To ascertain the value of annual mass roentgenographic screening, the Cooperative Study Group has collected the most important data about treatment results recorded in the main chest clinics in the GDR between 1949 and 1974. The study covers 13,293 operations and 10,838 resections in patients with lung cancer, representing nearly 90% of all patients with lung tumors treated surgically up to 1974. The cases were grouped according to mode of detection, i.e., by screening or by clinical symptoms. The latter group included those cases detected by chance, independent of periodic screening.

Surgical Treatment and Survival From 1949 to 1974, operations were performed on a total of 7,988 patients whose cancer was discovered through screening and 5,305 with clinical disease. In the period preceding sys- tematic screening, no significant difference was detected between the two groups in the total number of operations and resections performed. But over the last fifteen years of the study, there was an obvious increase in the total number of operations and resections among the cases detected through screening (Table 1). Resection rates were higher in the screened group; the differences are highly significant in all periods ( p S 0.001 by chi-square test).

There was also a significant increase in the total number of three- and five-year survivors, especially in the screened group (Table 2). The crude three- and five-year survival rates improved in both groups. But in the later periods (1963 to 1968), the five-year survival rates were more favorable in the screened group than in

406 0003-4975/78/0026-0504$01.25 @ 1978 by W. Widow

407 Roentgenographic Screening for Lung Cancer

Table 1 . Operations Performed for Lung Cancer during the Study Period

Screened Group Clinical Group

Resections Resections No. of No. of

Period Operations No. Y O Operations No. YO

1957-58 1959-60 1961-62 1963-64 1965- 66 1967-68 1969-70 1971-72 1973-74

1949-74

166 368 532 784 968

1,202 1,161 1,286 1,361

7,988

132 312" 439 657 850

1,065 1,035 1,157 1,170"

6,961

80 85 83 84 88 89 89 89 86

269 361 404 404 465 607 617 657 709

5,305

193 262" 268 269 339 446 485 508 55ga

3,877

72 73 66 67 73 73 79 77 79

"Compared with clinical cases, the increase in number of resections performed in the screened group during the periods 1959-60 to 1973-74 is highly significant ( p S 0.001 by chi-square test).

Table 2. Three- and Five-Year Survival Rates


Survival Survival

No. of 3 Yr 5 Yr No. of 3 Yr 5 Yr Resec- Resec-

Period tions No. YO No. Y O tions No. YO No. O h

1949-52 8 4 50 3 38 98 19 19 14 14 1953-54 51 20 39 18 35 216 70 32 59 27 1955-56 85 31 36 22 26 235 70 30 50 21 1957-58 132 52 39 40 30 193 53 27 38 20 1959-60 312 110 35 82 26 262 85 32 72 28 1961-62 439 188 43 151 34= 268 101 38 79 29 a

1963-64 657 292 44 233 35" 269 104 39 73 27" 1965-66 850 408 48 322 3Sa 339 132 39 93 27" 1967-68 1,065 455 43 363 34= 446 167 37 135 30" 1969-70 1,035 502 48 485 192 40

"The differences between the two groups are highly significant ( p S 0.001 by chi-square test).

the clinical group. Because more than two- thirds of the survivors were survey cases, the favorable survival in this group decisively af- fects the overall results. From 1961 to 1968, the mortality rate at the third and the fifth year was nearly 10% in both groups. But because the average age in the survey group was higher and because it contained more high-risk cases, the two groups had a different life expectancy. Therefore, the relative survival of patients in the screened group is seen to be still more favorable.

Site of Tumor and Lymph Node Involvement Nearly 75% of the patients in the screened group had peripheral lesions, whereas in the clinical group the proportion with peripheral lesions ranged from 36 to 49% (Table 3). Begin- ning with 1959, the differences are highly significant. Still more decisive is the increase in total number of peripheral lesions in the screened group from 1957-58 to 1973-74 (screened group, from 90 to 918 cases; clinical group, from 71 to 275 cases). The fact that in the period 1967-68 there were more central lesions

408 The Annals of Thoracic Surgery , Vol 26 No 5 November 1978

Table 3 . Location of Tumors

Period


Central Peripheral Central Peripheral

No. Y O No. Y O No. Y O No. Y O

1957-58 42 32 90 68 122 63 71 37 1959-60 104 33 208 67" 167 64 95 36" 1961-62 141 32 298 68" 154 57 114 43" 1963-64 175 27 482 73 " 170 63 99 37a 1965-66 208 24 642 76" 202 60 137 40" 1967-68 310 29 755 71 " 250 56 196 44a 1969-70 266 26 769 74" 256 53 229 4 7" 1971-72 266 23 891 77" 278 55 230 45" 1973- 74 252 22 918 78 a 283 51 275 49 " 1949- 74 1,816 26 5,145 74a 2,250 58 1,627 42"

aDifferences are highly significant ( p < 0.001 by chi-square test).

in the screened group than among clinical patients (308 versus 250) is interesting, too. This is an indication that the conditions for detection of central cancers by roentgenographic screening are not so unfavorable as has been assumed by many authors.

The five-year survival rate for patients with central lesions has been between 20 and 29% in both groups, whereas that for patients with peripheral lesions detected by screening was 39% from 1963 to 1968, with a total of 743 survivors against only 140 in the clinical group.

As for lymph node involvement, the total number and proportion of localized cases was much higher in the screened group. The five- year survival rate for patients with localized disease was 45% in the screened group and 39% in the clinical group from 1963 to 1968; this difference is significant ( p < 0.01 by chi- square test). Much more impressive is the total number of survivors with localized cancers in the screened group.

Type of Resection In connection with the increased incidence of localized and peripheral lesions, the proportion of lobectomies performed was much higher in the screened group (Table 4). The five-year survival rate of 39 to 40% (1963 to 1968) in patients who had lobectomy is more favorable than that of patients treated with pneumonec-

tomy; the differences are highly significant in the screened group and significant in the clinical group ( p < 0.001 and 0.01, respectively, by chi-square test). Furthermore, it should not be overlooked that lobectomy provides better pulmonary efficiency than pneumonectomy.

Limited excisions (wedge resections) were done mainly to keep the operative risk low in older patients with small peripheral lesions. The total number and proportion of such cases is increasing, and the five-year survival has ex- ceeded expectation.

Distribution by Age The proportion of patients older than 65 years in the screened group was 18% from 1949 to 1968 and 32% for the period 1973-74; for the clinical group these figures are 11 and 25%, respectively. The five-year survival rates of patients in the higher age ranges in the screened group were better on the whole than the survival rates for all age groups among the clinical cases (Table 5). Survival among patients under 50 years is not so poor as is generally assumed.

Distribution by Sex The ratio of men to women in the screened group was 9: 1 and in the clinical group, 19: 1; this difference is readily understandable because the proportion of peripheral lesions is


Table 4 . Five-Year Survival by Type of Resection

Period Pneumonectomy Lobectomy Wedge Resection

SCREENED GROUP

1959-62 21% (581270) 36% (1651458) 43% (10123) 1963-66 28% (1031367) 40% (42511,064) 37% (28176) 1967-68 17% (411242) 39% (2861732) 38% (35191) 1969-70“ ( . . ,1250) ( . . .1739) ( . . .146) 1971-72” ( . . ,1257) ( . . ,1818) ( . . .182) 1973-74 a ( . . ,1209) ( . . ,1822) ( . . ,1139)

CLINICAL GROUP

1959-62 26% (811312) 32% (691215) (113) 1963-66 23% (691296) 31 ‘/o (911292) 25% (5120) 1967-68 26% (551212) 33 ‘/o (74122 1) 46% (6113) 1969-70” ( . . ,1226) ( . . .1239) ( . . ,120) 1971-72 a ( . . ,1221) ( . . ./267) ( . . ,120) 1973-74 a ( . . .1245) ( . . ,1270) ( . . .143)

“Survival rates not yet available.

Table 5. Five-Year Survival by Age

Period S39 vr 40-49 vr 50-59 vr 60-64 vr 65-69 vr 270 vr

SCREENED GROUP

1949-66 37% (15140) 39% (661169) 36% (39611,106) 34% (2811835) 30% (1021345) 30% (12140) 1967-68 27% (7126) 33% (24173) 35% (1291372) 37% (1211325) 30% (671223) 27% (12145)

CLINICAL GROUP

1949-66 30% (9130) 28% (661237) 26O/0 (2441933) 23% (1171512) 23% (351149) 26% (5119) 1967-68 29% (5117) 33% (18155) 35% (541154) 29% (391133) 20% (15175) 25% (3112)

higher in women than in men. There were also some differences in survival rates between men and women: the five-year survival rate in the screened group for cases detected from 1964 to 1968 was 34.9% (700 of 2,004 cases) for men and 42.7% (117 of 274) for women; in the clinical group it was 28.6% (251 of 879 cases) for men and 38.6% (17 of 44 cases) for women.

survived five years, whereas in the clinical group only 15 (9%) of 167 who had resection for small cell carcinoma survived five years. This difference is highly significant ( p d 0.001 by chi-square test). Therefore, it is possible by roentgenographic screening to detect a higher proportion of otherwise prognostically unfavorable tumor types at a stage in which they are still localized to the lung. The improved

Histological Considerations survival of patients with undifferentiated car- The well-known fact that patients with his- cinoma detected by radiological screening has tologically differentiated types of cancer have a also been demonstrated by Ingberg and col- favorable prognosis needs no further discus- leagues L5]. sion. But among the undifferentiated types, it is possible to demonstrate that early detection of Comment small cell carcinomas improves survival re- The results of our study indicate that the value markably. Out of 229 cases detected by screen- of annual roentgenographic screening of the ing between 1949 and 1968, 49 patients (21%) chest for detection and treatment of lung

410 The Annals of Thoracic Surgery Vol 26 No 5 November 1978

cancer, especially in men past the age of 40 years, is no longer questionable [21. The increase in total number of operations, resections, and five-year survivors is mainly the result of screening. The high number of resections in the screened group with an excellent five-year survival rate (1965 to 1968; 685 of 1,915 in the screened group, or 36Y0, and 228 of 785 clinical patients, or 29%) determines the overall results. Among 275 patients who had resection in 1960, 75 survived five years or more. The number of new cases of lung cancer in patients under the age of 70 years registered by the Cancer Regis- try of the GDR in 1960 was 3,684; therefore, the 75 patients represent an absolute survival of only 2%. Among 834 patients who underwent resection in 1968, 275 survived five years or more; the incidence of new cases in patients under the age of 70 years was 4,702 that year, so the absolute survival was nearly 6%.

This situation constituted a promising be- ginning [6, 71. But as demonstrated by Table 1, there has been no further increase in the total number of operations and resections done since 1969, especially in the screened group. This stagnation in the number of operations is due to a growing reluctance in recent years to undertake lung screening-because of the overall decrease in pulmonary tuberculosis-and to a failure in some districts to maintain the one- year screening schedule; since 1970, only 60 to 75% of the adult male population has had a chest roentgenogram annually [lo].

It is obvious that annual screening of the whole adult population is no longer necessary. But to ensure earlier detection of lung cancer in the future, the performance of lung screening individualized in terms of a person’s risk of lung cancer is desirable. The program in the GDR has been reorganized, and the performance of lung screening is now based on the following recommendations [14]:

Nonsmokers, persons who have smoked fewer than 100,000 cigarettes, and women: biannual screening

Persons who have smoked between 100,000 and 200,000 cigarettes: annual screening if possible

Persons who have smoked more than 200,000 cigarettes: definitely annual screening

High-risk groups (professional exposure to car- cinogens; heavy smokers): semiannual screening including a cytological test of the sputum

Persons at risk include men aged 40 to 70 years. Men who are in excellent health should be ex- amined up to the age of 75 years. This differentiated approach and the full exploitation of all diagnostic and surgical facilities will guarantee further improvement in the overall results.

Retrospective studies of screening roentgenograms have clearly shown that a minimum of 20% of cancers are overlooked on studies performed one or in some instances two years earlier [6]. The proportion of such cases has been even higher in certain studies [ll, 121. From 1966 to 1970, nearly 35% of all new cases of lung cancer registered by the Central Cancer Regis- try of the GDR [lo] were detected by screening (e.g., 1966: 2,318 of 6,553 cases). Continued screening would enable detection of 40% of cases or more, particularly in those age groups curable by surgery. Furthermore, in the period in which these results were achieved, it was generally unknown whether or not annual screening of the chest influences survival rates in lung cancer. Therefore surgical treatment was not infrequently postponed, or even re- fused, especially in older people [131.

A trend toward broader indications for opera- tion and resection has been recognizable. This can be concluded from the steady increase in the proportion of patients above the age of 65 years in both the screened and the clinical group and from the observation that there has been only a leveling off and no decrease in the total number of operations performed despite a drop in the number of persons undergoing chest screening in recent years. Therefore, it should be possible to make both screening and treatment for lung cancer still more effective.

Similar conclusions have been drawn by other authors [2, 5, 9, 111. Absolute five-year survival rates of 10 to 15% can be achieved in men with lung cancer under the age of 70 years. The study of Ingberg and associates [5], based


on 1,293 patients with carcinoma of the lung, is very reliable. These cases were observed in a district of southern Finland with a population of about 500,000 during 1952 to 1970. The frequency of incidental findings increased from 11% in the period 1952 to 1964 to 28% in 1965 to 1970. Cancers detected incidentally were more frequently resectable. In the incidental group, the five-year survival rate was 15%; it was only 5% among symptomatic patients. In Brett’s con- trolled study [2] based on a test population of nearly 55,000 men, the five-year survival rate of patients with cancer of the lung was 6% (5 of 77) in the control group and 15% (15 of 101) in the study group. Chest roentgenograms had been offered to the study group at six-month intervals over a period of three years. In the study of Nash and associates [91 the survey group was not clearly defined, and the Philadelphia Pul- monary Neoplasm Research Project [12] had a very small test population, but both studies as well as the analysis of Veeze [ l l ] give some indication that a carefully designed roentgenographic detection program can be useful. Investi- gations to determine the additional value of sputum cytology studies, especially for the detection of central lesions in high-risk groups (men over 45 years of age who smoke at least one pack of cigarettes a day), are still in progress [l, 3, 81.

Lung cancer is the most frequent form of carcinoma in men, and its incidence in all age groups continues to increase, as shown by the records of our governmental cancer registry (Figure). These data demonstrate that among a group of 1,000 men aged 50 years, 40 to 50 will be afflicted with lung cancer in the following twenty years [4]. If there is a further rise in incidence, this number will exceed 50 cases, especially in heavy smokers. This is an alarming situation we will have to cope with.

Combined methods of treatment (preopera- tive or postoperative irradiation, additional chemotherapy) have failed to improve cure rates [13]. Radiotherapy alone is only palliative in most instances. For the near future, further improvement in the overall results can be ex- pected only if the following principles are observed:

600

500

LOO

300

200

100

0

age groups

d 1972 1969 1966 1960

9

lncidence by age group of new cases of lung cancer per 100,000 population in the years 1960, 1966, 1969, and 1972 in the GDR.

Differentiated regular roentgenographic screening (biannual, annual, semiannual) of men aged between 40 and 70 years (or older if they are in good health), the frequency dependent on their tobacco consumption.

Accurate evaluation of mass roentgenograms and acceleration of diagnostic procedures.

Closer surveillance of high-risk groups during the intervals between screening and effective dissemination of information to the public.

Full exploitation of all surgical modalities now available.

References 1. Baker RR, Marsh BR, Frost JK, et al: Detection

and treatment of early lung cancer. Ann Surg 179313, 1974

2. Brett GZ: Earlier diagnosis and survival in lung cancer. Br Med J 4260, 1969

3. Fontana RS, Sanderson DR, Miller WE, et al: The Mayo Lung Project: preliminary report of ”Early Cancer Detection Phase.” Cancer 30:1373, 1972

4. Herold H-J: Haufigkeit, Behandlung und Uber- leben beim Bronchialkarzinom unter besond- erer Berucksichtigung der Rontgenreihenunter- suchungen, in Symposium uber den Lungen- krebs. Edited by W Widow. Berlin, Akademie Verlag, 1976, pp 149-163

5 . Ingberg MV, Klossner I, Linna MI, et al: Facilities for surgery and survival prospects in lung carcinoma. Scand J Thorac Cardiovasc Surg 6297, 1972

6. Kooperative Studie: Die Bedeutung von jahr- lichen Rontgenreihenuntersuchungen fur die Erfassung und Behandlung des Bronchial- karzinoms. Dtsch Ges Wesen 28:2410. 1973

412 The Annals of Thoracic Surgery Vol 26 No 5 November 1978

7. Kooperative Studie: Die Bedeutung von jahr- lichen Rontgenreihenuntersuchungen fur die Erfassung und Behandlung des Bronchial- karzinoms, in Symposium uber den Lungen- krebs. Edited by W Widow. Berlin, Akademie Verlag, 1976, pp 165-179

8. Melamed M, Flehinger B, Miller D, et al: The National Lung Cancer Detection Program: preliminary results in New York City. Third In- ternational Symposium on the Detection and Prevention of Cancer. New York, 1976

9. Nash FA, Morgan J, Tomkins JG: South London Lung Cancer Study. Br Med J 2:715, 1968

10. Steinbriick P: Die bisherigen Ergebnisse und die weitere Perspektive der Rontgenreihenunter- suchungen bei der Erfassung gut- und bosartiger Erkrankungen der Lunge, in Symposium uber den Lungenkrebs. Edited by W Widow. Berlin, Akademie Verlag, 1976, pp 137-147

11. Veeze P: The use of mass radiography for the detection of lung cancer, in Proceedings of the Second International Symposium on Cancer De- tection and Prevention, Bologna, 1973 (Intema- tional Congress Series No. 322). Amsterdam, Ex- cerpta Medica, 1974, 166-172

12. Weiss W, Boucot KR: The Philadelphia Pulmo- nary Neoplasm Research Project. Arch Intem Med 134:306, 1974

13. Widow W, Matthes TH: Die chirurgische Be- handlung des Bronchialkarzinoms, in Sym- posium uber den Lungenkrebs. Edited by W Widow. Berlin, Akademie Verlag, 1976, pp 75-90

14. Wilde J: Risikogruppen-Fruherfassung beim Lungenkrebs, in Symposium uber den Lungen- krebs. Edited by W Widow. Berlin, Akademie Verlag, 1976, pp 185-193

Participating lnvesf igators W. Widow, M.D.; F. Anstett, M.D.; M. Bartel, M.D.; W. Barth, M.D.; A. Baudrexl, M.D.; L. Baudrexl, M.D.; L. Bergmann, M.D.; U. Botzke, M.D.; G. Dippmann, M.D.; H. Eule, M.D.; H.-J. Herold, M.D.; H. Kalkowski, M.D.; B. Klar, M.D.; A. Kriiger, M.D.; D. Kurpat, M.D.; Th. Matthes, M.D.; D. Nicolai, M.D.; H. G. Pannwitz, M.D.; R. Panzner, M.D.; G. Rothe, M.D.; H. Rupprecht, M.D.; Th. Scharkoff, M.D.; G. Schoefer, M.D.; H. Siegert, M.D.; W. van de Kamp, M.D.; D. Vieritz, M.D.; H. Voigt, M.D.; J . Weber, M.D.; J. Wilde, M.D.; Th. Becker, M.D.; W. Menne, M.D.; K.-H. Roemer, M.D.; G. Reppin, M.D.; W. Schmitt, M.D.; K. L. Schober, M.D.; W. Usbeck, M.D.; and U. Scheler, M.D.

roentgenographic chest screening in the detection and survival of patients with lung cancer

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