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Results of treatment of primary carcinoma of the lung
Results of treatment of primary carcinoma of the lung Analysis of 3,000 cases Three thousand patients with primary carcinoma of the lung entered in the Armed Forces Central Medical Registry are reported. Forty-one per cent had squamous cell, 28.5 per cent adenocarcinoma, 25.2 per cent small cell liindifferentiated, and 4.9 per cent miscellaneous cell types. When first seen, 71.1 per cent had no organ metastases and 50.6 per cent no lymph node metastases. Over-all survival rate was 18.2 per cent at 5 years and 14.5 per cent at 10 years. Survival following definitive resection, palliative resection, definitive radiation, palliative radiation, and chemotherapy was determined both in the presence of mediastinal nodal involvement and in the absence of mediastinal nodal involvement. Where resection for cure could be carried out, 5 year survival rates of 48.8 per cent were possible. The factors affecting this improved outlook in our military population are discussed and, in general, appear to be related to a ready accessibility of medical care and the necessity, because of global commitments, of establishing an early diagnosis. Cell type exerted some influence on survival, but the major determinant appeared to be the absence of involved nodes at the time of the operation.
William Stanford, M.D., Charles G. Spivey, Jr., M.D., Gordon L. Larsen, M.D., James A. Alexander, M.D., and William J. Besich, San Antonio, Texas
V_^ancer, other than superfical skin cancer and carcinoma in situ of the cervix, affects 654,000 Americans annually and is the second leading cause of death in the United States today. Lung cancer accounts for 21 per cent of cancer in men and 5 per cent of cancer in women and is the causative agent for 31 per cent of male cancer deaths and 10 per cent of female cancer deaths—an incidence 14 times that reported 40 years ago. In 1974, the American Cancer Society estimated 83,000 persons would develop cancer of the lung and 75,000 of these would die from their disease.1 In an attempt to define the present status of treatment for lung carcinoma, the records of 3,000 patients entered in the Armed Forces Central Medical Registry as of June, 1975, were reviewed. The Central Medical Registry, From the Thoracic Surgery Service, Wilford Hall United States Air Force Medical Center. Lackland Air Force Base, Texas, and the Central Medical Registry, Brooks Air Force Base, Texas. Received for publication May 14, 1976. Accepted for publication June 11. 1976. Address for reprints: William Stanford, Colonel, USAF (MC), Box 369112. Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236.
located at Brooks Air Force Base, Texas, has been in existence since 1972 and has accumulated data back through 1951. It receives input from Army, Navy, and Air Force hospitals world wide. These records form the basis of this report. Explanation of terms Nodal involvement. This term refers to lymph node involvement only. It does not include organ metastases, as these are coded separately. A patient with no lymph node involvement could conceivably have organ metastases. First-level nodal involvement. This term refers to hilar and/or mediastinal involvement only. It does include involvement in nodes that are intraparenchymal, since differentiation between these nodes and a more extensive involvement in nodes of the hilum or the ipselateral or contralateral mediastinum was not possible from the hospital record. By definition, it excludes all patients with nodal involvement beyond the confines of the mediastinum. Definitive surgery. This is surgery carried out for cure as opposed to palliation and includes those cases in which all identifiable tumor has been removed. 44 1
The Journal of Thoracic and Cardiovascular Surgery
4 4 2 Stanford et al.
Table I. Total group treatment categories Category
No.
No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above
485 981 83 114 747 230 360
Total
3,000
Table II. Bronchogenic and squamous cell treatment categories Category No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above Total
No.
195 415 33 55 343 60 130 1,231
Table HI. Adenocarcinoma treatment categories Category
No.
No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above
363 32 14 141 81 109
Total
865
125
Definitive radiation (radiation for cure). This category includes those patients in whom radiation was used as a primary treatment modality. Here, radiation was given with the expectation of achieving a cure and not for palliation, as would be the case in patients having only a partial removal of their tumor. (These latter patients would be classified under the palliative radiation heading.) In the definitive radiation category would be patients suspected of having microscopic invasion beyond the lines of resection and those with tumors involving only intraparenchymal nodes where the radiotherapist elected to treat in the event of unrecognized residual microscopic involvement. Adenocarcinoma. This group includes 119 patients with alveolar cell carcinoma.
Table IV. Small celllundifferentiated treatment categories Category
No.
No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above
154 116 13 42 244 82 105
Total
756
Table V. Five-year survival rates following resection
Author Maloney et al.13 Steele et al.16 Weiss9 Dillon and Postlethwait17 Overholt et al.18 Fuller3 Berrino et al.10 Kirklin et al.19 Brown5 Paulson4 Jones et al." Jensik et al. 20 Calif. Tumor Registry15 Shields et al.12 Brock21 Stanford
Survival, No. of patients resection for in series cure (9c) 16,107 392 833 566
37.0
Survival, resection palliation (9c) 8.0
29.0
1,851 266 405 767 162 1,911 358 119 273
41.0
2,348 293 3,000
33.7
13.2
37.0
24.5 22.0
36.0 27.5 41.5
42.0
26.0
56.4 32.2
48.8
Survival, over-all resection (9c)
4.7
26.2 32.0 41.3
Small cell/undifferentiated group. This group includes those tumors categorized as small cell, large cell, oat cell, and undifferentiated cell types. Survival curves. All survival curves are computed via the life-table method of Berkson and Gage2 with the curve being continued until either the population becomes zero or the 10 year end point is reached. Since the patient is entered into the Registry as soon as the diagnosis is made, the survival rate includes the operative mortality rate from the diagnostic or therapeutic procedure. Clinical material As of June 30, 1975, over 3,000 patients with primary carcinoma of the lung had been entered into the
Volume 72 Number 3 September, 1976
Primary carcinoma of lung
443
100
%SURVIVAl CASES
5YR.
■ TOTAL POPULATION
3000
18.21
14.47
"NEGATIVE NODES
1517
28.87
23.81
■ POSITIVE
1069
10.09
6.91
In LEVEL NODES
IOYR.
111
o
ez u a.
Fig. 1. Carcinoma of the lung. Breakdown by nodal involvement. Armed Forces Central Medical Registry. Data from the last 3,000 of these cases form this report. There were 2,344 male patients and 656 female patients. Ages ranged from 10 through 99 years with a mean age of 52.84 years. Seven patients were less than 20 years of age when first diagnosed. One had squamous cell, 3 had undifferentiated, and 3 had a miscellaneous cell type. When first seen, 2,133 patients (71.1 per cent) had no organ metastases, 856 (28.5 per cent) had distant organ metastases, and the status of 11 patients was unknown. No evidence of lymph node metastasis was present in 1,5! 7 patients (50.6 per cent). One thousand sixty-nine (35.6 per cent) had only first-level nodal involvement and 403 (13.4 per cent) had extension beyond the first-level nodes—the status of 11 patients
was unknown. Hence, 86.2 per cent had no nodal involvement or involvement of only mediastinal nodes. Twelve hundred twenty-four patients had some form of resection, for a resectability rate of 40.8 per cent; 1,776 (59.2 per cent) were deemed inoperable because of tumor location, nodal involvement, or distant organ metastases. Twelve hundred thirty-one (41.0 per cent) had squamous cell carcinoma, 865 adenocarcinoma (28.5 per cent), 756 small cell/undifferentiated (25.2 per cent), and 148 a miscellaneous cell type (4.9 per cent). Two hundred seventeen patients had multiple primary lesions. The status of 83.5 per cent of these patients was known at the 5 year period and all deaths except 117 were due to the primary disease process.
The Journal of Thoracic and Cardiovascular Surgery
4 4 4 Stanford et al.
100
8 CASES ■TOTAL
POPULATION
•DEFINITIVE " PALLIATIVE 'DEFINITIVE "PALLIATIVE
SURGERY SURGERY RADIATION RADIATION
' CHEMOTHERAPY
%SURVIVAL 5YR.
10YR.
14.47
3000
18.21
1027
48.76
3862
197
4.70
4.70
122
708
708
1055
170
.27
437
3.83
2 59
Fig. 2 Carcinoma of the lung. Breakdown by treatment. Survival The survival rate of the entire population was 18.2 per cent at 5 years and 14.5 per cent at 10 years (Fig. 1). When first-level nodes were not involved, the 5 and 10 year survival rates were 28.9 and 23.8 per cent, respectively. When these nodes were involved, the survival rates dropped to 10.1 and 6.9 per cent. The specific treatment for each patient is listed in Table I. Since a number of patients underwent several modalities of treatment, the survival rate was calculated to include all patients undergoing the treatment modality, and it is for this reason the totals in Fig. 2 will differ from those noted in Table I. In the over-all group the definitive surgery 5 and 10 year survival rates (1,027 patients) were 48.8 and 38.6
per cent. In the definitive radiation group (122 patients), survival rates were 7.1 and 7.1 per cent. When palliative surgery, palliative radiation, or chemotherapy was given, the 5 and 10 year survival rates were below 5 per cent. More meaningful might be the survival rates of each major cell type analyzed with regard to the treatment modality. Table II shows the treatment breakdown of the 1,231 patients with squamous cell carcinoma, whereas Fig. 3 shows survival rates for the specific treatment modality. The 5 year survival rate varied from 47.6 per cent with definitive resection to 2.3 per cent with palliative radiation. Intermediate in the treatment modalities were palliative surgery 6.3 per cent, definitive radiation 5.0 per cent, and chemo-
Volume 72 Number 3 September, 1976
Primary carcinoma of lung
445
100
, TOTAL
POPULATION
_
436
47.55
37 2 7
PALLIATIVE SURGERY
79
6.32
6.32
61
5.04
5.04
<49
2.27
1.86
132
652
5.22
„ DEFINITIVE E
% SURVIVAL SYR 10 YR 18.45 14.58
SURGERY
, DEFINITIVE _
CASES 1231
PALIIATIVE
RADIATION RADIATION
Fig. 3. Bronchogenic and squamous cell carcinoma of the lung. therapy 6.5 per cent. Over-all survival rate was 18.5 per cent. In adenocarcinoma, the treatment modalities are listed in Table III. Survival rate, listed in Fig. 4, was 50.8 per cent with definitive surgery. Comparable survival rate for definitive radiation (14 patients) was 21.1 per cent with no patients followed beyond 60 months. Survival rate for palliative surgery was 3.3 per cent with no patients beyond 72 months, and for palliative radiation 1.5 per cent with all patients dead after 84 months. In the chemotherapy group, survival rate was 2.7 per cent with no patients alive after 96 months. Over-all survival rate was 23.3 per cent. The small cell/undifferentiated group underwent treatment as per Table IV. Survival rate as seen in Fig. 5 was 27.2 per cent for definitive surgery. Definitive
radiation had a survival rate of 7.6 per cent with no patients entered beyond 96 months. In the palliative surgery group, all patients but one were dead by 24 months and that patient had been entered only 24 months. Palliative radiation had 1.2 per cent alive at 5 years and chemotherapy 2.8 per cent alive at 5 years, but none was followed beyond 72 months. Over-all survival rate was 6.6 per cent. Discussion Survival in lung cancer is dependent upon early diagnosis before spread to mediastinal nodes or distant organs has occurred. When these circumstances are present and the tumor can be totally removed, survival rates of 48.8 per cent are possible. Even in the small cell/undifferentiated group which most physicians feel
The Journal of Thoracic and Cardiovascular Surgery
4 4 6 Stanford et al.
100
o/o SURVIVAL 10 YR 5YR
i
24
36
48
60
72
MONTHS
96
108
120
Fig. 4. Adenocarcinoma of the lung. offers the poorest prognosis, a survival rate of 27.2 per cent was possible. As expected, squamous cell and adenocarcinoma offer the better prognoses. The slightly higher survival rate present in our adenocarcinoma group may be a reflection of the fact that 14.3 per cent of these patients had alveolar cell carcinoma, a subtype which appears to give a better prognosis.3, 4 One must guard against overoptimism, however, since the presence in the resected specimen of incidentally involved nodes dropped the survival rate in the definitive resection group from 48.8 per cent to 30.0 per cent. Patients undergoing incomplete resection and those in whom involved nodes still remained had a much poorer prognosis—4.7 per cent. Most of these patients were either given postoperative radiation or chemotherapy or both, but this appeared to have little effect on the eventual outcome.
Of special interest was survival by cell type in patients undergoing definitive resection where nodal involvement was found incidentally in the specimen. As previously mentioned, the over-all 5 year survival rate in this group was 30.0 per cent. In squamous cell, the comparable 5 year survival rate was 33.8 per cent, in adenocarcinoma it was 29.4 per cent, and in small cell/undifferentiated 13.2 per cent. These figures are somewhat higher than expected, but may be a reflection of our selection process in that we were unable to differentiate those patients with involved intraparenchymal nodes from those with more widespread mediastinal metastases. It should also be noted that in most cases definitive surgery would not be carried out in the face of mediastinal involvement. Comparison of survival figures in lung carcinoma is difficult. Some authors report only over-all survival rates, others survival with resection, not differentiating
Volume 72 Number 3 September, 1976
Primary carcinoma of lung
447
lOOi
90] %SURVIVAL
80
\ \ \ \
\ \
h*
60
ec u
50
z 111 o
5 YR
TOTAL POPULATION
756
6.60
5.94
•DEFINITIVE SURGERY
124
27.18
23.98
A
11
70
CASES
B • \
D \ H
1
B
\
37
+
" DEFINITIVE
RADIATION
44
7.62
*
E
PALLIATIVE
RADIATION
336
1.21
1.21
F
CHEMOTHERAPY
154
2.75
+
C \
D \ \
10 YR
PALLIATIVE SURGERY '
+
CL
40
It \ \ 1
>i
■ * \\ l 1 \\\ 1
30
^\. 'v
1 *\\l
^XN.
\ v\
20
\ \*x \ \1 \\ * \ \ 1
\t
1
10 O
\
V TV
X
_^„
N:«N
^ j .
12
24
36
,— — D
, _
A
1_
48
60 72 MONTHS
84
96
108
E 120
Fig. 5. Undifferentiated carcinoma of the lung. between resection for cure and palliative resection, and yet others report survival rates following lobectomy or pneumonectomy without stating the extent of the lesion. In an attempt to obtain some type of perspective, 5 year survival rates following resection as reported by several authors were compared in Table V. As can be seen, survival rates following resection for cure (the best category) varied from 29 to 56 per cent with the palliative resection survival rate being much lower. The over-all survival rate with resection appears to vary between 22 and 41 per cent. Also of interest were some series of resected patients tabulated as to 5 year survival by cell type (Table VI). As expected, squamous cell and adenocarcinoma offer the better prognoses. Influencing all the above statistics is the fact that our data come from military hospitals world wide. As such, they represent a select group of patients who have
ready accessibility to medical care, to periodic physical examinations, and to frequent chest roentgenograms. Also, selection plays an important role in that the patient's work-up often included brain and bone scans, bronchoscopic evaluations, cervical mediastinal exploration (CME), bronchial brushing, and sometimes angiograms—factors which lower the operability rate but improve resectability. In addition, the diminished cost of medical care in the military and the necessity of having our personnel capable for world-wide duty exert an influence toward the earlier removal of a solitary pulmonary nodule than might occur in the civilian community. These factors are probably reflected in the fact that 71.1 per cent of our patients had no organ metastases when first seen and that over 50 per cent of this series had no evidence of lymph node involvement. While our resectability rate of 40.8 per cent is in keeping with other reported series (Table VII), it is of
448
The Journal of Thoracic and Cardiovascular Surgery
Stanford et al.
Table VI. Five-year survival rates according to cell type
Author
No. of patients in series
Dillon and Postlethwait17 Fuller3 Jones et al." Feinstein et al.22 Campobasso et al.23 Weiss9 Paulson4 Shields et al.12 Sullivan24 Minton et al.25 Kirklinet al.19 Stanford
566 266 358 449 554 833 1,911 2,348 594 1,884 767 3,000
Resected patients, curative and palliative Squamous cell (%)
Adenoc arcinoma
<%)
Undifferentiated (Vc)
37,0 26.0 16.1 34.3 21.1 26.0 26.8
32.0 40.0 6.8 19.7 12.7 20.0 24.3
18.0 12.0 3.1 8.3-16.2 8.4 6.0-21.0 22.4
42.0 41.1
54.0 42.8
15.0-30.0 21.4
All treatment modalities f9c) 3.1 25.0 9.0 24.4 15.7 6.5 15.0 18.2
Table VII. Patients who had exploratory operations and resection
Author 15
Maloney et al. Steele et al. 16 Weiss9 Dillon and Postlethwait" Paulson"1 Fuller3 Berrino et al.10 Martini et al.26 Calif. Tumor Registry1' Okinaka and Gray7 Biel and Tortolani27 Kirklin et al. 19 Brock21 Feinstein et al.22 Overholt et al.B Stanford
No. of patients in series 16,107 392 833 566 1,911 266 405 799 100 662 68 767 293 449 3,000 3,000
Per cent explored 54.0 65.6 36.7
43.0 43.0 82.0 48.0 23.0 46.0 74.0
note that all but 197 of the 1,224 lesions that could be resected were resected for cure. Hence, few palliative operations were carried out. Other factors such as the age and sex distribution appear to be similar to those reported elsewhere—with an average age in the sixth decade and an incidence of squamous cell approaching 50 per cent, adenocarcinoma 20 per cent, and undifferentiated 30 per cent. 5 - 9 Last, some authors believe the presence or absence of lymph node metastases and not cell type are the major determinants of survival. 1 1 - 1 3 Our data would tend to support that concept. Paulson 4 reported in his series that only 15 per cent had localized disease, that 30 per cent had regional involvement, and that over 50
Average per cent resected 29.0 94.4 43.6 17.3 40.0 70.3 29.0 25.0 18.0 32.0 57.0 29.0 36.0 60.0 40.8
Resection Per cent curative
Per cent palliative
78.6
15.:
5.0
13.0
24.0
5.0
39.0 34.2
21.0 6.5
per cent had distant metastases when first seen. National averages appear similar, with 20 per cent having localized disease and 40 per cent distant metastases. 7 ' 15 Our figures appear better in this regard and again emphasize the fact that earlier detection can be associated with improved survival, irrespective of cell type. We wish to thank the Biometrics Division, School of Aerospace Medicine, Brooks Air Force Base, Texas, for the statistical analyses. REFERENCES 1 Cancer—Facts and Figures, Bull. Am. Cancer Soc, 1974. 2 Berkson, J., and Gage, R. P.: Calculation of Survival Rates for Cancer, Proc. Mayo Clin. 25: 270, 1950.
Volume 72 Number 3 September, 1976
Primary carcinoma of lung
3 Fuller, J.: Surgical Treatment of Lung Cancer. Five Year Follow-up of 266 Patients, Minn. Med. 56: 1024, 1973. 4 Paulson. D. L.: A Philosophy of Treatment for Bronchogenic Carcinoma, Ann. Thorac. Surg. 5: 289, 1968. 5 Brown, J. H.: Results of Resection for Bronchogenic Carcinoma, Med. J. Aust. 2: 71, 1971. 6 Lee, Y. N.: Prognostic Factors in Surgical Treatment of Bronchogenic Carcinoma, Surg. Gynecol. Obstet. 135: 961, 1972. 7 Okinaka, A. J., and Gray, G. F.: Carcinoma of the Lung at the New York Hospital—Cornell Medical Center (1964-1968), Proc. Seventh Natl. Cancer Conf., 1973, p. 743. 8 Overholt, R. H., Oliynik, P. N., and Cody, B.: The Current Status of Primary Carcinoma of the Lung, Proc. Clin. Cancer 4: 211, 1970. 9 Weiss, W.: Operative Mortality and Five Year Survival Rates in Men with Bronchogenic Carcinoma, Chest 66: 483, 1974. 10 Berrino, F., Musso, M., and Campobasso, O.: Pathological Factors in Survival of Lung Tumors: Local Extent, Size, and Nodal Involvement, Br. J. Cancer 25: 669, 1971. 11 Jones, J. C , Kern, W. H., Chapman, N. D., Meyer, B. W., and Lindesmith, G. G.: Long-Term Survival after Surgical Resection for Bronchogenic Carcinoma, J. THORAC. CARDIOVASC. SURG. 54: 383,
1967.
12 Shields, T. W., Yee, J., Conn, J. H., and Robinette, C. D.: . Relationship of Cell Type and Lymph Node Metastasis to Survival after Resection Bronchial Carcinoma, Presentation Soc. Thorac. Surg. Meeting, Montreal, January, 1975. 13 Paulson, D. L.: Operability versus Resectability in Bronchogenic Carcinoma. Ann. Thorac. Surg. 3: 177, 1967. 14 Rubin, P.: Bronchogenic Carcinoma Stage I. Current Concepts of Cancer, No. 10, J. A.M. A. 195: 154, 1966. 15 Maloney. J. V., Bennett, L. R., Longmire, W. P., Madden, S. C , Rigler, L. G., Simmons, Oh.h., Steele, J. D., Stein, J. J., Troup, G. M., and Weber, A. P.:
16
17 18
19
20
449
Carcinoma of the Lung—The UCLA Interdepartmental Conference Ann. Intern. Med. 64: 165, 1966. Steele, J. D., Kleitsch, W. P., Dunn, J. E., and Buell, P.: Survival in Males with Bronchogenic Carcinoma Resected as Asymptomatic Solitary Pulmonary Nodules, Ann. Thorac. Surg. 2: 368, 1966. Dillon, M. L., and Postlethwait, R. W.: Carcinoma of the Lung, Ann. Thorac. Surg. 11: 193, 1971. Overholt, R. H., Neptune, W. B., and Ashraf, M. M.: Primary Cancer of the Lung: A 42-year Experience, Presentation Soc. Thorac. Surg. Meeting, Montreal, January, 1975. Kirklin, J. W., McDonald, J. R., Clagett, D. T., Moersch, H. J., and Gage, R. P.: Bronchogenic Carcinoma: Cell Type and Other Factors Relating to Prognosis, Surg. Gynecol. Obstet. 100: 429, 1955. Jensik, R. J., Faber, L. P., Milloy, F. J., and Monson, D. O.: Segmental Resection for Lung Cancer—a Fifteen-Year
Experience, J.
SURG. 66: 563,
THORAC.
CARDIOVASC.
1973.
21 Brock, Lord: Long Survival after Operation for Cancer of the Lung, Br. J. Surg. 62: 1, 1975. 22 Feinstein, A. R., Gelfman, N. A., and Yesner, R.: The Diverse Effects of Histopathology on Manifestations and Outcome of Lung Cancer, Chest 66: 225, 1974. 23 Campobasso, O., Invernizzi, B., Musso, M., and Berrino, F.: Survival Rates of Long Cancer According to Histological Type, Br. J. Cancer 29: 240, 1974. 24 Sullivan, H. J.: Bronchogenic Carcinoma: The True Story, Geriatrics 28: 140, 1973. 25 Minton, J. P., Sabback, M. S., and Oberle, K. V.: Lung Cancer Survival—The Ohio State University Hospitals, Ohio State Med. J. 69: 27, 1973. 26 Martini, N., Cliffton, E. E., and Beattie, E. J.: Survival of Lung Cancer Patients vis-a-vis Therapy and Cell Type, Proc. Seventh Natl. Cancer Conf., 1973, p. 739. 27 Beil, A. R., and Tortolani, A. J.: Survival of Lung Cancer Patients in a Community Hospital, Proc. Seventh Natl. Cancer Conf., 1973, p. 747.
William Stanford, M.D., Charles G. Spivey, Jr., M.D., Gordon L. Larsen, M.D., James A. Alexander, M.D., and William J. Besich, San Antonio, Texas
V_^ancer, other than superfical skin cancer and carcinoma in situ of the cervix, affects 654,000 Americans annually and is the second leading cause of death in the United States today. Lung cancer accounts for 21 per cent of cancer in men and 5 per cent of cancer in women and is the causative agent for 31 per cent of male cancer deaths and 10 per cent of female cancer deaths—an incidence 14 times that reported 40 years ago. In 1974, the American Cancer Society estimated 83,000 persons would develop cancer of the lung and 75,000 of these would die from their disease.1 In an attempt to define the present status of treatment for lung carcinoma, the records of 3,000 patients entered in the Armed Forces Central Medical Registry as of June, 1975, were reviewed. The Central Medical Registry, From the Thoracic Surgery Service, Wilford Hall United States Air Force Medical Center. Lackland Air Force Base, Texas, and the Central Medical Registry, Brooks Air Force Base, Texas. Received for publication May 14, 1976. Accepted for publication June 11. 1976. Address for reprints: William Stanford, Colonel, USAF (MC), Box 369112. Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236.
located at Brooks Air Force Base, Texas, has been in existence since 1972 and has accumulated data back through 1951. It receives input from Army, Navy, and Air Force hospitals world wide. These records form the basis of this report. Explanation of terms Nodal involvement. This term refers to lymph node involvement only. It does not include organ metastases, as these are coded separately. A patient with no lymph node involvement could conceivably have organ metastases. First-level nodal involvement. This term refers to hilar and/or mediastinal involvement only. It does include involvement in nodes that are intraparenchymal, since differentiation between these nodes and a more extensive involvement in nodes of the hilum or the ipselateral or contralateral mediastinum was not possible from the hospital record. By definition, it excludes all patients with nodal involvement beyond the confines of the mediastinum. Definitive surgery. This is surgery carried out for cure as opposed to palliation and includes those cases in which all identifiable tumor has been removed. 44 1
The Journal of Thoracic and Cardiovascular Surgery
4 4 2 Stanford et al.
Table I. Total group treatment categories Category
No.
No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above
485 981 83 114 747 230 360
Total
3,000
Table II. Bronchogenic and squamous cell treatment categories Category No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above Total
No.
195 415 33 55 343 60 130 1,231
Table HI. Adenocarcinoma treatment categories Category
No.
No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above
363 32 14 141 81 109
Total
865
125
Definitive radiation (radiation for cure). This category includes those patients in whom radiation was used as a primary treatment modality. Here, radiation was given with the expectation of achieving a cure and not for palliation, as would be the case in patients having only a partial removal of their tumor. (These latter patients would be classified under the palliative radiation heading.) In the definitive radiation category would be patients suspected of having microscopic invasion beyond the lines of resection and those with tumors involving only intraparenchymal nodes where the radiotherapist elected to treat in the event of unrecognized residual microscopic involvement. Adenocarcinoma. This group includes 119 patients with alveolar cell carcinoma.
Table IV. Small celllundifferentiated treatment categories Category
No.
No treatment Definitive surgery Palliative surgery Definitive radiation Palliative radiation Chemotherapy Combinations of the above
154 116 13 42 244 82 105
Total
756
Table V. Five-year survival rates following resection
Author Maloney et al.13 Steele et al.16 Weiss9 Dillon and Postlethwait17 Overholt et al.18 Fuller3 Berrino et al.10 Kirklin et al.19 Brown5 Paulson4 Jones et al." Jensik et al. 20 Calif. Tumor Registry15 Shields et al.12 Brock21 Stanford
Survival, No. of patients resection for in series cure (9c) 16,107 392 833 566
37.0
Survival, resection palliation (9c) 8.0
29.0
1,851 266 405 767 162 1,911 358 119 273
41.0
2,348 293 3,000
33.7
13.2
37.0
24.5 22.0
36.0 27.5 41.5
42.0
26.0
56.4 32.2
48.8
Survival, over-all resection (9c)
4.7
26.2 32.0 41.3
Small cell/undifferentiated group. This group includes those tumors categorized as small cell, large cell, oat cell, and undifferentiated cell types. Survival curves. All survival curves are computed via the life-table method of Berkson and Gage2 with the curve being continued until either the population becomes zero or the 10 year end point is reached. Since the patient is entered into the Registry as soon as the diagnosis is made, the survival rate includes the operative mortality rate from the diagnostic or therapeutic procedure. Clinical material As of June 30, 1975, over 3,000 patients with primary carcinoma of the lung had been entered into the
Volume 72 Number 3 September, 1976
Primary carcinoma of lung
443
100
%SURVIVAl CASES
5YR.
■ TOTAL POPULATION
3000
18.21
14.47
"NEGATIVE NODES
1517
28.87
23.81
■ POSITIVE
1069
10.09
6.91
In LEVEL NODES
IOYR.
111
o
ez u a.
Fig. 1. Carcinoma of the lung. Breakdown by nodal involvement. Armed Forces Central Medical Registry. Data from the last 3,000 of these cases form this report. There were 2,344 male patients and 656 female patients. Ages ranged from 10 through 99 years with a mean age of 52.84 years. Seven patients were less than 20 years of age when first diagnosed. One had squamous cell, 3 had undifferentiated, and 3 had a miscellaneous cell type. When first seen, 2,133 patients (71.1 per cent) had no organ metastases, 856 (28.5 per cent) had distant organ metastases, and the status of 11 patients was unknown. No evidence of lymph node metastasis was present in 1,5! 7 patients (50.6 per cent). One thousand sixty-nine (35.6 per cent) had only first-level nodal involvement and 403 (13.4 per cent) had extension beyond the first-level nodes—the status of 11 patients
was unknown. Hence, 86.2 per cent had no nodal involvement or involvement of only mediastinal nodes. Twelve hundred twenty-four patients had some form of resection, for a resectability rate of 40.8 per cent; 1,776 (59.2 per cent) were deemed inoperable because of tumor location, nodal involvement, or distant organ metastases. Twelve hundred thirty-one (41.0 per cent) had squamous cell carcinoma, 865 adenocarcinoma (28.5 per cent), 756 small cell/undifferentiated (25.2 per cent), and 148 a miscellaneous cell type (4.9 per cent). Two hundred seventeen patients had multiple primary lesions. The status of 83.5 per cent of these patients was known at the 5 year period and all deaths except 117 were due to the primary disease process.
The Journal of Thoracic and Cardiovascular Surgery
4 4 4 Stanford et al.
100
8 CASES ■TOTAL
POPULATION
•DEFINITIVE " PALLIATIVE 'DEFINITIVE "PALLIATIVE
SURGERY SURGERY RADIATION RADIATION
' CHEMOTHERAPY
%SURVIVAL 5YR.
10YR.
14.47
3000
18.21
1027
48.76
3862
197
4.70
4.70
122
708
708
1055
170
.27
437
3.83
2 59
Fig. 2 Carcinoma of the lung. Breakdown by treatment. Survival The survival rate of the entire population was 18.2 per cent at 5 years and 14.5 per cent at 10 years (Fig. 1). When first-level nodes were not involved, the 5 and 10 year survival rates were 28.9 and 23.8 per cent, respectively. When these nodes were involved, the survival rates dropped to 10.1 and 6.9 per cent. The specific treatment for each patient is listed in Table I. Since a number of patients underwent several modalities of treatment, the survival rate was calculated to include all patients undergoing the treatment modality, and it is for this reason the totals in Fig. 2 will differ from those noted in Table I. In the over-all group the definitive surgery 5 and 10 year survival rates (1,027 patients) were 48.8 and 38.6
per cent. In the definitive radiation group (122 patients), survival rates were 7.1 and 7.1 per cent. When palliative surgery, palliative radiation, or chemotherapy was given, the 5 and 10 year survival rates were below 5 per cent. More meaningful might be the survival rates of each major cell type analyzed with regard to the treatment modality. Table II shows the treatment breakdown of the 1,231 patients with squamous cell carcinoma, whereas Fig. 3 shows survival rates for the specific treatment modality. The 5 year survival rate varied from 47.6 per cent with definitive resection to 2.3 per cent with palliative radiation. Intermediate in the treatment modalities were palliative surgery 6.3 per cent, definitive radiation 5.0 per cent, and chemo-
Volume 72 Number 3 September, 1976
Primary carcinoma of lung
445
100
, TOTAL
POPULATION
_
436
47.55
37 2 7
PALLIATIVE SURGERY
79
6.32
6.32
61
5.04
5.04
<49
2.27
1.86
132
652
5.22
„ DEFINITIVE E
% SURVIVAL SYR 10 YR 18.45 14.58
SURGERY
, DEFINITIVE _
CASES 1231
PALIIATIVE
RADIATION RADIATION
Fig. 3. Bronchogenic and squamous cell carcinoma of the lung. therapy 6.5 per cent. Over-all survival rate was 18.5 per cent. In adenocarcinoma, the treatment modalities are listed in Table III. Survival rate, listed in Fig. 4, was 50.8 per cent with definitive surgery. Comparable survival rate for definitive radiation (14 patients) was 21.1 per cent with no patients followed beyond 60 months. Survival rate for palliative surgery was 3.3 per cent with no patients beyond 72 months, and for palliative radiation 1.5 per cent with all patients dead after 84 months. In the chemotherapy group, survival rate was 2.7 per cent with no patients alive after 96 months. Over-all survival rate was 23.3 per cent. The small cell/undifferentiated group underwent treatment as per Table IV. Survival rate as seen in Fig. 5 was 27.2 per cent for definitive surgery. Definitive
radiation had a survival rate of 7.6 per cent with no patients entered beyond 96 months. In the palliative surgery group, all patients but one were dead by 24 months and that patient had been entered only 24 months. Palliative radiation had 1.2 per cent alive at 5 years and chemotherapy 2.8 per cent alive at 5 years, but none was followed beyond 72 months. Over-all survival rate was 6.6 per cent. Discussion Survival in lung cancer is dependent upon early diagnosis before spread to mediastinal nodes or distant organs has occurred. When these circumstances are present and the tumor can be totally removed, survival rates of 48.8 per cent are possible. Even in the small cell/undifferentiated group which most physicians feel
The Journal of Thoracic and Cardiovascular Surgery
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100
o/o SURVIVAL 10 YR 5YR
i
24
36
48
60
72
MONTHS
96
108
120
Fig. 4. Adenocarcinoma of the lung. offers the poorest prognosis, a survival rate of 27.2 per cent was possible. As expected, squamous cell and adenocarcinoma offer the better prognoses. The slightly higher survival rate present in our adenocarcinoma group may be a reflection of the fact that 14.3 per cent of these patients had alveolar cell carcinoma, a subtype which appears to give a better prognosis.3, 4 One must guard against overoptimism, however, since the presence in the resected specimen of incidentally involved nodes dropped the survival rate in the definitive resection group from 48.8 per cent to 30.0 per cent. Patients undergoing incomplete resection and those in whom involved nodes still remained had a much poorer prognosis—4.7 per cent. Most of these patients were either given postoperative radiation or chemotherapy or both, but this appeared to have little effect on the eventual outcome.
Of special interest was survival by cell type in patients undergoing definitive resection where nodal involvement was found incidentally in the specimen. As previously mentioned, the over-all 5 year survival rate in this group was 30.0 per cent. In squamous cell, the comparable 5 year survival rate was 33.8 per cent, in adenocarcinoma it was 29.4 per cent, and in small cell/undifferentiated 13.2 per cent. These figures are somewhat higher than expected, but may be a reflection of our selection process in that we were unable to differentiate those patients with involved intraparenchymal nodes from those with more widespread mediastinal metastases. It should also be noted that in most cases definitive surgery would not be carried out in the face of mediastinal involvement. Comparison of survival figures in lung carcinoma is difficult. Some authors report only over-all survival rates, others survival with resection, not differentiating
Volume 72 Number 3 September, 1976
Primary carcinoma of lung
447
lOOi
90] %SURVIVAL
80
\ \ \ \
\ \
h*
60
ec u
50
z 111 o
5 YR
TOTAL POPULATION
756
6.60
5.94
•DEFINITIVE SURGERY
124
27.18
23.98
A
11
70
CASES
B • \
D \ H
1
B
\
37
+
" DEFINITIVE
RADIATION
44
7.62
*
E
PALLIATIVE
RADIATION
336
1.21
1.21
F
CHEMOTHERAPY
154
2.75
+
C \
D \ \
10 YR
PALLIATIVE SURGERY '
+
CL
40
It \ \ 1
>i
■ * \\ l 1 \\\ 1
30
^\. 'v
1 *\\l
^XN.
\ v\
20
\ \*x \ \1 \\ * \ \ 1
\t
1
10 O
\
V TV
X
_^„
N:«N
^ j .
12
24
36
,— — D
, _
A
1_
48
60 72 MONTHS
84
96
108
E 120
Fig. 5. Undifferentiated carcinoma of the lung. between resection for cure and palliative resection, and yet others report survival rates following lobectomy or pneumonectomy without stating the extent of the lesion. In an attempt to obtain some type of perspective, 5 year survival rates following resection as reported by several authors were compared in Table V. As can be seen, survival rates following resection for cure (the best category) varied from 29 to 56 per cent with the palliative resection survival rate being much lower. The over-all survival rate with resection appears to vary between 22 and 41 per cent. Also of interest were some series of resected patients tabulated as to 5 year survival by cell type (Table VI). As expected, squamous cell and adenocarcinoma offer the better prognoses. Influencing all the above statistics is the fact that our data come from military hospitals world wide. As such, they represent a select group of patients who have
ready accessibility to medical care, to periodic physical examinations, and to frequent chest roentgenograms. Also, selection plays an important role in that the patient's work-up often included brain and bone scans, bronchoscopic evaluations, cervical mediastinal exploration (CME), bronchial brushing, and sometimes angiograms—factors which lower the operability rate but improve resectability. In addition, the diminished cost of medical care in the military and the necessity of having our personnel capable for world-wide duty exert an influence toward the earlier removal of a solitary pulmonary nodule than might occur in the civilian community. These factors are probably reflected in the fact that 71.1 per cent of our patients had no organ metastases when first seen and that over 50 per cent of this series had no evidence of lymph node involvement. While our resectability rate of 40.8 per cent is in keeping with other reported series (Table VII), it is of
448
The Journal of Thoracic and Cardiovascular Surgery
Stanford et al.
Table VI. Five-year survival rates according to cell type
Author
No. of patients in series
Dillon and Postlethwait17 Fuller3 Jones et al." Feinstein et al.22 Campobasso et al.23 Weiss9 Paulson4 Shields et al.12 Sullivan24 Minton et al.25 Kirklinet al.19 Stanford
566 266 358 449 554 833 1,911 2,348 594 1,884 767 3,000
Resected patients, curative and palliative Squamous cell (%)
Adenoc arcinoma
<%)
Undifferentiated (Vc)
37,0 26.0 16.1 34.3 21.1 26.0 26.8
32.0 40.0 6.8 19.7 12.7 20.0 24.3
18.0 12.0 3.1 8.3-16.2 8.4 6.0-21.0 22.4
42.0 41.1
54.0 42.8
15.0-30.0 21.4
All treatment modalities f9c) 3.1 25.0 9.0 24.4 15.7 6.5 15.0 18.2
Table VII. Patients who had exploratory operations and resection
Author 15
Maloney et al. Steele et al. 16 Weiss9 Dillon and Postlethwait" Paulson"1 Fuller3 Berrino et al.10 Martini et al.26 Calif. Tumor Registry1' Okinaka and Gray7 Biel and Tortolani27 Kirklin et al. 19 Brock21 Feinstein et al.22 Overholt et al.B Stanford
No. of patients in series 16,107 392 833 566 1,911 266 405 799 100 662 68 767 293 449 3,000 3,000
Per cent explored 54.0 65.6 36.7
43.0 43.0 82.0 48.0 23.0 46.0 74.0
note that all but 197 of the 1,224 lesions that could be resected were resected for cure. Hence, few palliative operations were carried out. Other factors such as the age and sex distribution appear to be similar to those reported elsewhere—with an average age in the sixth decade and an incidence of squamous cell approaching 50 per cent, adenocarcinoma 20 per cent, and undifferentiated 30 per cent. 5 - 9 Last, some authors believe the presence or absence of lymph node metastases and not cell type are the major determinants of survival. 1 1 - 1 3 Our data would tend to support that concept. Paulson 4 reported in his series that only 15 per cent had localized disease, that 30 per cent had regional involvement, and that over 50
Average per cent resected 29.0 94.4 43.6 17.3 40.0 70.3 29.0 25.0 18.0 32.0 57.0 29.0 36.0 60.0 40.8
Resection Per cent curative
Per cent palliative
78.6
15.:
5.0
13.0
24.0
5.0
39.0 34.2
21.0 6.5
per cent had distant metastases when first seen. National averages appear similar, with 20 per cent having localized disease and 40 per cent distant metastases. 7 ' 15 Our figures appear better in this regard and again emphasize the fact that earlier detection can be associated with improved survival, irrespective of cell type. We wish to thank the Biometrics Division, School of Aerospace Medicine, Brooks Air Force Base, Texas, for the statistical analyses. REFERENCES 1 Cancer—Facts and Figures, Bull. Am. Cancer Soc, 1974. 2 Berkson, J., and Gage, R. P.: Calculation of Survival Rates for Cancer, Proc. Mayo Clin. 25: 270, 1950.
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Primary carcinoma of lung
3 Fuller, J.: Surgical Treatment of Lung Cancer. Five Year Follow-up of 266 Patients, Minn. Med. 56: 1024, 1973. 4 Paulson. D. L.: A Philosophy of Treatment for Bronchogenic Carcinoma, Ann. Thorac. Surg. 5: 289, 1968. 5 Brown, J. H.: Results of Resection for Bronchogenic Carcinoma, Med. J. Aust. 2: 71, 1971. 6 Lee, Y. N.: Prognostic Factors in Surgical Treatment of Bronchogenic Carcinoma, Surg. Gynecol. Obstet. 135: 961, 1972. 7 Okinaka, A. J., and Gray, G. F.: Carcinoma of the Lung at the New York Hospital—Cornell Medical Center (1964-1968), Proc. Seventh Natl. Cancer Conf., 1973, p. 743. 8 Overholt, R. H., Oliynik, P. N., and Cody, B.: The Current Status of Primary Carcinoma of the Lung, Proc. Clin. Cancer 4: 211, 1970. 9 Weiss, W.: Operative Mortality and Five Year Survival Rates in Men with Bronchogenic Carcinoma, Chest 66: 483, 1974. 10 Berrino, F., Musso, M., and Campobasso, O.: Pathological Factors in Survival of Lung Tumors: Local Extent, Size, and Nodal Involvement, Br. J. Cancer 25: 669, 1971. 11 Jones, J. C , Kern, W. H., Chapman, N. D., Meyer, B. W., and Lindesmith, G. G.: Long-Term Survival after Surgical Resection for Bronchogenic Carcinoma, J. THORAC. CARDIOVASC. SURG. 54: 383,
1967.
12 Shields, T. W., Yee, J., Conn, J. H., and Robinette, C. D.: . Relationship of Cell Type and Lymph Node Metastasis to Survival after Resection Bronchial Carcinoma, Presentation Soc. Thorac. Surg. Meeting, Montreal, January, 1975. 13 Paulson, D. L.: Operability versus Resectability in Bronchogenic Carcinoma. Ann. Thorac. Surg. 3: 177, 1967. 14 Rubin, P.: Bronchogenic Carcinoma Stage I. Current Concepts of Cancer, No. 10, J. A.M. A. 195: 154, 1966. 15 Maloney. J. V., Bennett, L. R., Longmire, W. P., Madden, S. C , Rigler, L. G., Simmons, Oh.h., Steele, J. D., Stein, J. J., Troup, G. M., and Weber, A. P.:
16
17 18
19
20
449
Carcinoma of the Lung—The UCLA Interdepartmental Conference Ann. Intern. Med. 64: 165, 1966. Steele, J. D., Kleitsch, W. P., Dunn, J. E., and Buell, P.: Survival in Males with Bronchogenic Carcinoma Resected as Asymptomatic Solitary Pulmonary Nodules, Ann. Thorac. Surg. 2: 368, 1966. Dillon, M. L., and Postlethwait, R. W.: Carcinoma of the Lung, Ann. Thorac. Surg. 11: 193, 1971. Overholt, R. H., Neptune, W. B., and Ashraf, M. M.: Primary Cancer of the Lung: A 42-year Experience, Presentation Soc. Thorac. Surg. Meeting, Montreal, January, 1975. Kirklin, J. W., McDonald, J. R., Clagett, D. T., Moersch, H. J., and Gage, R. P.: Bronchogenic Carcinoma: Cell Type and Other Factors Relating to Prognosis, Surg. Gynecol. Obstet. 100: 429, 1955. Jensik, R. J., Faber, L. P., Milloy, F. J., and Monson, D. O.: Segmental Resection for Lung Cancer—a Fifteen-Year
Experience, J.
SURG. 66: 563,
THORAC.
CARDIOVASC.
1973.
21 Brock, Lord: Long Survival after Operation for Cancer of the Lung, Br. J. Surg. 62: 1, 1975. 22 Feinstein, A. R., Gelfman, N. A., and Yesner, R.: The Diverse Effects of Histopathology on Manifestations and Outcome of Lung Cancer, Chest 66: 225, 1974. 23 Campobasso, O., Invernizzi, B., Musso, M., and Berrino, F.: Survival Rates of Long Cancer According to Histological Type, Br. J. Cancer 29: 240, 1974. 24 Sullivan, H. J.: Bronchogenic Carcinoma: The True Story, Geriatrics 28: 140, 1973. 25 Minton, J. P., Sabback, M. S., and Oberle, K. V.: Lung Cancer Survival—The Ohio State University Hospitals, Ohio State Med. J. 69: 27, 1973. 26 Martini, N., Cliffton, E. E., and Beattie, E. J.: Survival of Lung Cancer Patients vis-a-vis Therapy and Cell Type, Proc. Seventh Natl. Cancer Conf., 1973, p. 739. 27 Beil, A. R., and Tortolani, A. J.: Survival of Lung Cancer Patients in a Community Hospital, Proc. Seventh Natl. Cancer Conf., 1973, p. 747.